EA006080B1

EA006080B1 - 6-position substituted indoline, production and use thereof as a medicament

Info

Publication number: EA006080B1
Application number: EA200200380A
Authority: EA
Inventors: Армин Хеккель; Геральд Юрген Рот; Райнер Вальтер; Якобус Ван-Мэл; Норберт Редеманн; Ульрике Тонтш-Грунт; Вальтер Спевак; Франк Хильберг
Original assignee: Бёрингер Ингельхайм Фарма Гмбх Унд Ко. Кг.
Priority date: 1999-10-13
Filing date: 2000-10-09
Publication date: 2005-08-25
Also published as: WO2001027081A1; CN100455568C; NO2015009I1; PL207445B1; DK1224170T5; AU1023301A; BRPI0014735B8; LU92681I9; PE20010671A1; JP2003511441A; BE2015C018I2; EA200200380A1; BRPI0014735A; HK1052505B; IL148756A; CA2387013C; EG25931A; CY1110067T1; RS51013B; IL148756A0

Abstract

The invention relates to a 6-substituted indoline of formula (I), wherein R1 to R5 and X are as defined in claim 1, isomers and salts of said compound, in particular physiologically compatible salts of said compound having pharmacologically important characteristics, in particular inhibiting action on different receptor-tyrosine kinases and cyclin/CDK complexes in addition to inhibiting the proliferation of endothelial cells and different tumor cells. The invention also relates to medicaments containing said compounds, the use of said compounds and a method for the production thereof.

Description

The present invention relates to the newly substituted in position 6 of the indolinone of the General formula

their tautomers, their diastereomers, their enantiomers, their mixtures and their salts, primarily their physiologically acceptable salts, which have valuable properties.

The above compounds of general formula I, in which Κι represents a hydrogen atom or a prodrug residue, possess valuable pharmacological properties, primarily inhibiting effect on various kinases, mainly receptor tyrosine kinases, such as UE6PK2, ΡΌΘΡΚα, ΡΌΟΡΚβ, ΡΟΡΚ1, ΡΟΡΚ3,, ΗΕΚ2 , YuR1K and ΗΟΡΚ, as well as on the complexes of JUICE (from the English. Sus1n bepebepaktek, cyclin-dependent kinases), such as SEK1. CEC2, CEC3. SEK4. ΟΌΙ <5. SEK6, SOK7, SEK8 and SEK9 with their specific cyclins (A, B1, B2, C, Ό1, Ό2, Ό3, E, Ρ, O1, O2, H, I and K), and for viral cyclin (see b. Mepd1ao, I. Uy1odu 71 (3), 1984-1991 (1997)), as well as on the proliferation of cultured human cells, especially endothelial cells, for example during angiogenesis (development of blood vessels), and on the proliferation of other cells, especially tumor cells .

The remaining compounds of the above general formula I, in which K! has different values from the hydrogen atom and the prodrug residue; they are valuable intermediate products for the preparation of the above compounds.

In accordance with this object of the present invention, the above compounds of general formula I, among which are compounds in which Κι represents a hydrogen atom or a prodrug residue, possess valuable pharmacological properties, as well as drugs containing pharmacologically active compounds, the use of these compounds and their method receiving.

In the above general formula I

X means an oxygen or sulfur atom,

TO! It represents a hydrogen atom or a prodrug radical, such as C1 _-4 -alkoxycarbonyl or C _2-4 -alkanoyl,

K ₂ is a carboxy group, a linear or branched C _1-6 alkoxycarbonyl group, a C _4-7 cycloalkoxycarbonyl or aryloxycarbonyl, linear or branched S1-6alkoksikarbonilnuyu group, the alkyl moiety which is substituted in the terminal position by phenyl, heteroaryl, carboxy, C _1-3 alkoxycarbonyl, aminocarbonyl, C1 _-3 alkylaminocarbonyl or di- (C1 _-3 alkyl) aminocarbonyl, a linear or branched C2-6 alkoxycarbonyl group, the alkyl fragment of which is substituted in the terminal position by a chlorine atom, a hydroxy group, S1-3alkoksigruppoy, amino S1-3alkilaminogruppoy or di- (C1-3alkyl) amino, aminocarbonyl or methylaminocarbonyl group optionally substituted in the 2-position of the ethyl group by a hydroxy or C _1-3 alkoxy ethylaminocarbonyl group or, if R ₄ does not mean aminosulfonylphenyl or X - (C _1-5 alkyl) -C _1-3 alkylaminocarbonylphenyl, also means a di (C1 _-2 alkyl) aminocarbonyl group,

K ₃ means a hydrogen atom, C 1 _-6 alkyl, C _3-7 cycloalkyl, trifluoromethyl or heteroaryl, phenyl or naphthyl, mono- or disubstituted with a fluorine atom, chlorine, bromine or iodine, trifluoromethyl, C _1-3 alkyl or C _1-3 alkoxy group phenyl or naphthyl, while in the case of substitution by two groups, the substituents may be identical or different and the indicated unsubstituted as well as mono- and disubstituted phenyl and naphthyl may additionally be substituted with a hydroxy group, hydroxy-C1 _-3 alkyl or C1 _-3 alkoxy-C1 _-3 alkyl, cyano, carboxy, carboxy-C1-3 alkyl, C 1-3alkoxycarbonyl, aminocarbonyl, C1-3alkylaminocarbonyl or di- (C1-3alkyl) aminocarbonyl, nitro, amino, C _1-3 alkylamino, di- (C _1-3 alkyl) amino, or amino-C _1-3 alkyl,

C _1-3 alkylcarbonylamino, L- (C _1-3 alkyl) -C _1-3 alkylcarbonylamino, C _1-3 alkylcarbonylamino-C _1-3 alkyl, N- (0 _1-3 alkyl) -C _1-3 alkylcarbonylamino C _1-3 alkyl, C _1-3 alkylsulfonylamino, C _1-3 alkylsulfonylamino-C _1-3 alkyl, N- (0 _1-3 alkyl) -C _1-3 alkylsulfonylamino-C _1-3 alkyl or aryl-C1- 3 alkylsulfonylamino, cycloalkylamino, cycloalkylenimino, cycloalkyleniminocarbonyl, cycloalkylenimino-C _1-3 alkyl, cycloalkyleniminocarbonyl-C _1-3 alkyl or cycloalkylenimino sulfonylC1-3 alkyl in each case with 4-7 members and rings, with each of the methylene groups in position

- 1 006080 in a 6- or 7-membered cycloalkylenimino group can be replaced by an oxygen or sulfur atom, sulfinyl, sulfonyl, -ΝΗ- or -Y (C1 _- zalkyl) -, or heteroaryl or heteroaryl-C _1-3 alkyl,

I ₄ means C _3-7 cycloalkyl, while the methylene group in position 4 of the 6- or 7-membered cycloalkyl group may be substituted by an amino group, a C _1-3 alkylamino group or a di- (C _1-3 alkyl) amino group or replaced by -ΝΗ - or - ^ C _1-3 alkyl) -, or substituted by a group of I ₆ phenyl, which can additionally be mono- or disubstituted by a fluorine, chlorine, bromine or iodine atom, C _1-5 alkyl, trifluoromethyl, hydroxy, C _1-3 alkoxy, carboxy, C _1-3 alkoxycarbonyl, amino, acetylamino, C _1-3 alkylsulfonylamino, aminocarbonyl , S1-3alkilaminokarbonilom, di- (C1-3alkyl) aminocarbonyl, aminosulfonyl, S1-3alkilaminosulfonilom, di (C1-3alkyl) aminosulphonyl, nitro or cyano group, wherein the substituents may be identical or different, and

I ₆ means a hydrogen atom, fluorine, chlorine, bromine or iodine, cyano, nitro, amino, C 1-5 alkyl, C 3-7 cycloalkyl, trifluoromethyl, phenyl, tetrazolyl or heteroaryl, a group of the formula

in which in each case the hydrogen atoms linked to the nitrogen atom can independently be replaced by C _1-3 alkyl, C _1-3 alkoxy group, C _1-3 alkoxy-C _1-3 alkoxy group, phenyl-C _1-3 alkoxy group , amino-C _2-3 alkoxy group, C _1-3 alkylamino-C _2-3 alkoxy group, di- (C _1-3 alkyl) amino-C ₂ - ₃ alkoxy group, phenyl-C _1-3 alkylamino C _2-3 alkoxy group, No (C _1-3 alkyl) phenyl-C _1-3 alkylamino-C _2-3 alkoxy group, C5-7 cycloalkylamino-C2-3 alkoxy group or C1-3 alkyl mercapto group, carboxy group, C1-4 alkoxycarbonyl, aminocarbonyl, C _1-3 alkylaminocarbonyl, no. (C _1-5 alkyl l) -C _1-3 alkylaminocarbonyl, phenyl-C _1-3 alkylaminocarbonyl, No. (C _1-3 alkyl) phenyl-C _1-3 alkylaminocarbonyl, piperazinocarbonyl or Ν (C _1-3 alkyl) piperazinocarbonyl, C _1-3 alkylaminocarbonyl or No. (C _1-5 alkyl) -C _1-3 alkylaminocarbonyl in which the alkyl moiety is substituted by a carboxy group or a C _1-3 alkoxycarbonyl or in position 2 or 3 is substituted by a di- (C _1-3 alkyl) amino group, piperazino group, no. ( C _1-3 alkyl) piperazino or 47-membered tsikloalkileniminogruppoy, C _3-7 cycloalkylcarbonyl, wherein the methylene group in position 4 of a 6- or 7-membered cycloalkyl, Nogo fragment can be substituted with amino, C _1-3 alkylamino or di- _(C1-3 alkyl) amino or substituted by -ΝΗ- or -MC | _-3 alkyl) -. 4-7-membered cycloalkylenimino group in which the methylene group bound to the imino group can be replaced by carbonyl or sulfonyl, or the cycloalkylene fragment can be condensed with a phenyl ring, or one or two hydrogen atoms in each case can be replaced with C _1-3 alkyl and / or the methylene group in each case in the 4 position of a 6 or 7-membered cycloalkylenimino group may be substituted by a carboxy group, C1 ₃ alkoxycarbonyl, aminocarbonyl, C _1-3 alkylaminocarbonyl, di- (C _1-3 alkyl) aminocarbonyl, phenyl-C _1-3 alkylamine Ogroup or No. (C _1-3 alkyl) phenyl-C _1-3 alkylamino or replaced by an oxygen or sulfur atom, sulfinyl, sulfonyl, -ΝΗ-, -MS _1-3 alkyl) -, - ^ phenyl) -, - ^ C _1-3 alkylcarbonyl) or - ^ benzoyl) -, substituted by a group I ₇ C _1-4 alkyl, where

I ₇ means C _4-7 cycloalkyl, while the methylene group in position 4 of the 6-or 7-membered cycloalkyl group may be substituted by an amino group, a C _1-3 alkylamino group or a di- (C _1-3 alkyl) amino group or is replaced by -ΝΗ - or -MS _1-3 alkyl) - or in a 5-7-membered cycloalkyl group, the group - (CH ₂ ) ₂ - can be replaced by the group -CO-ΝΗ-, the group - (CH ₂ ) ₃ - can be replaced by the group -ΝΗ-ί.Ό-ΝΗ- or -ί.Ό-ΝΗ-ί.Ό- or the group - (SI ₂ ) _4- can be replaced by the group -ΝΗ-ί.Ό-ΝΗ-ί.Ό-, wherein in each case bonded to the nitrogen atom, the hydrogen atom may be replaced by C _1-3 and keel, aryl, or heteroaryl, hydroxy or C _1-3 alkoxy, amino, _C1-7 alkylamino, di- _(C1-7 alkyl) amino, phenylamino, №fenil-C _1-3 alkylamino, phenyl-C _1-3 alkylamino-, No. (C _1-3 alkyl) phenyl-C _1-3 alkylamino or di- (phenyl-C _1-3 alkyl) amino group, w-hydroxy-C _2-3 alkylamino, No (C _1-3 alkyl) -sh-hydroxy-C _2-3 alkylamino-, di- (w-hydroxy-C _2-3 alkyl) amino-, di- (y-c (C _1-3 alkoxy) -C ₂ to ₃ alkyl) amino or no. (Dioxolan-2-yl) -C _1-3 alkylamino,

C _1-3 alkylcarbonylamino-C _2-3 alkylamino or C _1-3 alkylcarbonylamino-C _2-3 alkyl-No (C _1-3 alkyl) amino group,

C _1-3 alkylsulfonylamino, No. (C _1-3 alkyl) -C _1-3 alkylsulfonylamino, C _1-3 alkylsulfonylamino _2-3 alkylamino or C _1-3 alkylsulfonylamino-C ₂ - ₃ alkyl-No (C _{1 -3} alkyl) amino group, hydroxycarbonyl-C _1-3 alkylamino or NO (C _1-3 alkyl) hydroxycarbonyl-C _1-3 alkylamino group, guanidino, in which one or two hydrogen atoms in each case can be replaced by

C1-3 alkyl,

- 006080 group of the formula

-M (I ₈ ) -CO- (CH ₂ ) _P -Y ₉ (II), in which

By ₈ represents a hydrogen atom or a C1 _-3 alkyl, η represents the number 0, 1, 2 or 3 and

K ₉ is amino, C _1-4 alkylamino, di- (C _1-4 alkyl) amino, phenylamino, M- (C _1-4 alkyl) phenylamino, benzylamino, N- (C _{1- 4} alkyl) benzylamino or C _1-4 alkoxy group, 4-7-membered cycloalkylenimino group, in each case the methylene group in position 4 of the 6- or 7-membered cycloalkylenimino group can be replaced by an oxygen or sulfur atom, sulfinyl, sulfonyl, - ΝΗ-, -Y (C _1-3 alkyl) -, -N (phenyl) -, - ^ C _1-3 alkylcarbonyl) - or - ^ benzoyl) -, or, if η means 1, 2 or 3, is is also a hydrogen atom, a group of the formula

-ZHKYUMODTChOG-Yats (III), in which

K ₁₀ represents a hydrogen atom, C _1-3 alkyl, C _1-3 alkylcarbonyl, arylcarbonyl, phenyl-C _1-3 alkylcarbonyl, C _1-3 alkylsulfonyl, arylsulfonyl or phenyl-C _1-3 alkylsulfonyl, t represents the number 1 , 2, 3, or 4, o is the number 1, or, if t is one of the numbers 2, 3, or 4, is also the number 0 and

K. n represents an amino group, a C _1-4 alkylamino group, a di- (C _1-4 alkyl) amino, phenylamino, no. (C _1-4 alkyl) phenylamino, benzylamino, no. (C _1-4 alkyl) a benzylamino, C _1-4 alkoxy or C _1-3 alkoxy C _1-3 alkoxy group optionally substituted in the 1 position with a C _1-3 alkyl di- (C _1-4 alkyl) amino C _1-3 alkylamino group or 4 -7-membered cycloalkylenimino group, wherein the cycloalkylene moiety can be condensed with a phenyl ring or in each case the methylene group in position 4 of the 6- or 7-membered cycloalkylenimino group can be replaced by an oxygen atom yes or sulfur, sulfinyl, sulfonyl, -ΝΗ-, -MC | _-3 alkyl) -. -Mphenyl) -. - ^ C _1-3 alkylcarbonyl) - or - ^ benzoyl) -,

C _4-7 cycloalkylamino, C _4-7 cycloalkyl-C _1-3 alkylamino or C _4-7 cycloalkenylamino group in which the position 1 of the ring does not participate in the formation of a double bond, with these groups being optionally substituted in each case amine nitrogen atom With _5-7 cycloalkyl, C _2-4 alkenyl or C 1-4 alkyl,

A 4-7 membered cycloalkylenimino group in which the cycloalkylene moiety can be condensed with a phenyl group or with an optionally substituted fluorine, chlorine, bromine or iodine atom, a nitro group, a C1-3 alkyl, C1-3 alkoxy group or an amino group of an oxazolo, imidazolo, thiazolo, the pyridino, pyrazino or pyrimidine group and / or one or two hydrogen atoms in each case can be replaced by C _1-3 alkyl, C _5-7 cycloalkyl or phenyl and / or methylene group in position 3 of the 5-membered cycloalkylenimino group can be replaced hydroxy group guide hydroxy-C _1-3 alkyl, C _1-3 alkoxy or C _1-3 alkoxy-C _1-3 alkyl, in each case a methylene group in position 3 or 4, 6- or 7-membered tsikloalkileniminogruppy may be substituted with hydroxy, hydroxy- C _1-3 alkyl, C _1-3 alkoxy group, C _1-3 alkoxy-C _1-3 alkyl, carboxy group, C _1-4 alkoxycarbonyl, aminocarbonyl, C _1-3 alkylaminocarbonyl, di (C _1-3 alkyl) aminocarbonyl, phenyl-C _1-3 alkylamino or No. (C _1-3 alkyl) phenyl-C _1-3 alkylamino or replaced by an oxygen or sulfur atom, sulfinyl, sulfonyl, -ΝΗ-, - ^ C _1-3 alkyl -) -, ^ (phenyl) -, - ^ fen Il-C _1-3 alkyl -) -, - ^ C _1-3 alkylcarbonyl -) -, - ^ C _1-4 hydroxycarbonyl -) -, - ^ C _1-4 alkoxycarbonyl -) -, - ^ benzoyl -) - or - ^ phenyl-C _1-3 alkylcarbonyl -) -, while the methylene group bonded to the imine nitrogen atom of the cycloalkylamino group can be replaced by a carbonyl or sulfonyl or in a 5-7 membered monocyclic or condensed with a phenyl cycloalkylene amino group both bonded to the imine atom nitrogen methylene groups in each case can be replaced by carbonyl, or

K. ₆ means C _1-4 alkyl, which is substituted by a carboxy group, C _1-3 alkoxycarbonyl, aminocarbonyl, C _1-3 alkylaminocarbonyl or di (C _1-3 alkyl) aminocarbonyl or 4-7-membered cycloalkylene iminocarbonyl group, No. (C _1-3 alkyl) -C _2-4 alkanoylamino group, which in the alkyl fragment is additionally substituted by a carboxy group or C1-3 alkoxycarbonyl, a group of the formula

-Ν ^ ΧΟ- ^ ΗΧ, -Κβ (IV), in which

K ₁₂ represents a hydrogen atom, C _1-6 alkyl or C _3-7 cycloalkyl or substituted in the terminal position by phenyl, heteroaryl, trifluoromethyl, hydroxy group, C 1-3 alkoxy group, aminocarbonyl, C 1-4 alkylaminocarbonyl, di (C 1-4 alkyl) aminocarbonyl, C1-3 alkylcarbonyl, C1-3 alkylsulfonylamino, No. (C _1-3 alkyl) -C _1-3 alkylsulfonylamino, C _1-3 alkylaminosulfonyl or di- (C _1-3 alkyl) aminosulfonyl C _1-3 alkyl, p is the number 0 , 1, 2 or 3 and

K values above ₁₃ receives groups or K, if p denotes one of the numbers 1, 2 or 3, also represents a hydrogen atom,

- 3 006080 group of the formula

-M (K ₁ 4) - (CH ₂ ) _H - (CO) _G -K ₁₅ (V), in which

K ₁₄ represents a hydrogen atom, C _1-4 alkyl, C _1-3 alkylcarbonyl, arylcarbonyl, phenyl-C _1-3 alkylcarbonyl, heteroarylcarbonyl, heteroaryl-C _1-3 alkylcarbonyl, C _1-4 alkylsulfonyl, arylsulfonyl, phenyl-C _1-3 alkylsulfonyl, heteroarylsulfonyl or heteroaryl-C _1-3 alkylsulfonyl, is a number 1, 2, 3 or 4, g is a number 1 or, if C. | means one of the numbers 2, 3 or 4, is also the number 0 and

K. | ₅ takes the values of the above group K ₇ , a group of the formula

-Ν (Κ1 ₆ ) -δθ2-Κ17 (VI), in which

K ₁₆ represents a hydrogen atom or optionally substituted at the terminal position by a cyano group, a trifluoromethylcarbonylamino group or a No. (C _1-3 alkyl) trifluoromethylcarbonylamino group C _1-4 alkyl and

K ₁₇ is C _1-3 alkyl, substituted di- (C _1-3 alkyl) amino-C _1-3 alkylcarbonyl or di (C _1-3 alkyl) amino-C _1-3 alkylsulfonyl and di- (C _{1- 3} alkyl) aminocarbonyl-C _1-3 alkyl amino group or means No. (C _1-3 alkyl) -C _1-5 alkylsulfonylamino or No. (C _1-3 alkyl) phenylsulfonylamino, in which the alkyl fragment is additionally substituted by cyano or carboxy, with In this case, all single-bonded or condensed phenyl groups contained in the residues indicated for K ₆ may be disubstituted with a fluorine, chlorine or bromine atom. or iodine, C1-5 alkyl, trifluoromethyl, hydroxy, C1-3 alkoxy, carboxy, C1-3 alkoxycarbonyl, aminocarbonyl, C _1-4 alkylaminocarbonyl, di- (C _1-4 alkyl) aminocarbonyl, aminosulfonyl, C _1-3 alkylaminosulfonyl, di-aminocarbonyl, aminocarbonyl (C _1-3 alkyl) aminosulfonyl, C _1-3 alkylsulfonylamino, nitro or cyano groups, the substituents may be identical or different, or two adjacent hydrogen atoms of the phenyl groups may be replaced by a methylenedioxy group, and

K ₅ means a hydrogen atom or a C _1-3 alkyl, wherein the aryl group should be understood to be optionally mono- or disubstituted by a fluorine atom, chlorine, bromine or iodine, a cyano group, trifluoromethyl, a nitro group, a carboxy group, an aminocarbonyl, C _1-3 alkyl or C _1-3 alkoxy group phenyl or naphthyl, and the heteroaryl group should be understood as an optionally substituted monocyclic 5- or 6-membered heteroaryl group in the carbon skeleton of a C _1-3 alkyl, the 6-membered heteroaryl group containing one, two or three nitrogen atoms, and the 5-membered a roaryl group contains an imino group optionally substituted with C _1-3 alkyl or phenyl C _1-3 , an oxygen or sulfur atom or an imino group optionally substituted with C _1-3 alkyl or phenyl C _1-3 alkyl, and additionally a nitrogen atom or optionally substituted with C _1-3 alkyl or phenyl-C _1-3 alkyl imino group and two nitrogen atoms, and, in addition, with the indicated monocyclic heterocyclic groups, phenyl ring can be condensed through two adjacent carbon atoms, and the bond is carried out through the nitrogen atom or through the carbon atom of the heterocyclic moiety or of the condensed phenyl ring, hydrogen atoms in the indicated alkyl and alkoxy groups or in the alkyl fragments contained in the above for formula I groups can be partially or completely replaced by fluorine atoms under saturated alkyl groups present in the above groups and alkoxy moieties that contain more than 2 carbon atoms are also understood, unless otherwise indicated, their branched isomers, such as, for example, isopropyl, tert-butyl, isobutyl, and is hydrogen or a carboxy group is present linked to the nitrogen atom the hydrogen atom, for example an amino, imino or alkilaminoili Ν-saturated heterocycle, such as piperidinyl, in each case can be replaced by a cleavable ίη νίνο residue.

By the cleavable ίη νίνο residue from the imino or amino group is meant, for example, a hydroxy group, an acyl group such as benzoyl or pyridinoyl, or a C _1-16 alkanoyl group such as a formyl, acetyl, propionyl, butanoyl, pentanoyl or hexanoyl, allyloxycarbonyl group, S1-16alkoksikarbonilnaya group such as methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, tert-butoxycarbonyl, pentoxycarbonyl, hexyloxycarbonyl, octyloxycarbonyl, nonyloxycarbonyl, decyloxycarbonyl, undecyloxy carbonyl, dodecyloxycarbonyl or geksadetsiloksikarbonil, phenylC _1-6 alkoxycarbonyl group such as the benzyloxycarbonyl, phenylethoxycarbonyl or phenylpropoxycarbonyl, C _1-3 alkylsulfonyl-C _2-4 alkoxycarbonyl group, a C _1-3 alkoxy-C _2-4 alkoxy-C _2-4 alkoxycarbonyl group or group

K _e CO-O- (K _g CK ₈ ) -O-CO, in which K _e means C _1-8 alkyl, C _5-7 cycloalkyl, phenyl or phenyl-C _1-3 alkyl,

K _£ means a hydrogen atom, C _1-3 alkyl, C _5-7 cycloalkyl or phenyl and

- 4 006080

K _d means a hydrogen atom, C1. ₃ alkyl or K _e CO-O- (K _£ CK ₈ ) -O group, in which K _e -K ₈ have the values indicated above, in the case of the cleavable отη νίνο from the amino group of the residue, the phthalimido group is also meant ester residues can also be used as a transferable ίη νимойνο group.

Among the compounds of the general general formula I, a particular subgroup should be singled out in which X, K ₁ and K ₃ -K ₅ have the above values, and

K ₂ means a linear or branched C _1-6 alkoxycarbonyl group, a C _4-7 cycloalkoxycarbonyl or aryloxycarbonyl, a linear or branched C _1-6 alkoxycarbonyl group, the alkyl portion of which is substituted at the terminal position with phenyl, heteroaryl, carboxy, C 1-3 alkoxycarbonyl, and C 1–3 alkoxycarbonyl group. C1-3alkylaminocarbonyl or di- (C1-3alkyl) aminocarbonyl, a linear or branched C2-6 alkoxycarbonyl group, the alkyl fragment of which is substituted in the terminal position by a chlorine atom, a hydroxy group, a C1-3 alkoxy group, and minogroup, C _1-3 alkylamino or di- (C _1-3 alkyl) amino group, their tautomers, their diastereomers, their enantiomers, their mixtures and their salts.

As the second subgroup of compounds of the general formula I, the compounds in which X, K ₁ and K ₃ -K ₅ have the values indicated above, and

K ₂ means aminocarbonyl or methylaminocarbonyl, optionally substituted in position 2 of an ethyl group by a hydroxy group or a C _1-3 alkoxy group of an ethylaminocarbonyl or, if K ₄ does not mean aminosulfonylphenyl or X- (C _1-5 alkyl) -C _1-3 alkylaminocarbonyl, phenyl, also means di - (C _1-2 alkyl) aminocarbonyl, their tautomers, their diastereomers, their enantiomers, their mixtures and their salts.

As the third subgroup of compounds of the general formula I, it is particularly necessary to single out, in addition, compounds in which X, K ₁ -K ₃ and K ₅ have the above values, and

K ₄ means K ₇ - (C _1-4 alkyl) phenyl group, in which

K ₇ is amino, C _1-7 alkylamino, di- (C _1-7 alkyl) amino, phenylamino, L-phenyl-C _1-3 alkylamino, phenyl-C _1-3 alkylamino, X - (C _1-3 alkyl) phenyl-C _1-3 alkylamino or di (phenyl-C _1-3 alkyl) amino group, or a phenyl group substituted by a group of the formula

-X (K12) -CO- (CH2) p-Kl3 (IV), in which K ₁₂ , p and K ₁₃ have the above values, their tautomers, their diastereomers, their enantiomers, their mixtures and their salts.

Preferred compounds of general formula I are compounds in which K ₁ and K ₃ are as defined above, and X is an oxygen atom,

K ₂ means a carboxy group, a linear or branched C _1-6 alkoxycarbonyl group, a C _3-7 cycloalkoxycarbonyl or phenoxycarbonyl, a linear or branched C _1-3 alkoxycarbonyl group, the alkyl portion of which is substituted at the terminal position with phenyl, heteroaryl, carboxy, C _1-3 alkoxycarbonyl, aminocarbonyl, C _1-3 alkylaminocarbonyl or di- (C _1-3 alkyl) aminocarbonyl, a linear or branched C _2-3 alkoxycarbonyl group, the alkyl fragment of which is substituted in the terminal position by a chlorine atom, a hydroxy group, With _1-3 alkoxy group, amino group, C _1-3 alkylamino or di (C _1-3 alkyl) amino group, aminocarbonyl or methylaminocarbonyl, optionally substituted in position 2 of the ethyl group with a hydroxy group or C1-3 alkoxy group of ethylaminocarbonyl or, if K ₄ does not mean aminosulfonylphenyl or X- (C _1-5 alkyl) C _1-3 alkylaminocarbonylphenyl, also means di- (C _1-2 alkyl) aminocarbonyl,

K ₄ means C _3-7 cycloalkyl, wherein the methylene group in position 4 of the 6- or 7-membered cycloalkyl group may be substituted by an amino group, a C _1-3 alkylamino group or a di- (C _1-3 alkyl) amino group or is replaced by -ΝΗ - or -H (C _1-3 alkyl) -, or substituted by a K ₆ group phenyl, which can additionally be mono- or disubstituted with a fluorine, chlorine or bromine atom, C _1-3 alkyl, trifluoromethyl, hydroxy group, C _1-3 alkoxy group , carboxy, C _1-3 alkoxycarbonyl, amino, acetylamino, aminocarbonyl, C _1-3 alkylaminocarbonyl, di- (C _1-3 alk yl) aminocarbonyl, nitro or cyano, the substituents may be identical or different, and

K ₆ means a hydrogen atom, fluorine, chlorine, bromine or iodine, cyano, nitro, amino, C _1-5 alkyl, C _3-7 cycloalkyl, trifluoromethyl, phenyl, tetrazolyl or heteroaryl, a group of the formula

in which the hydrogen atom bound to the nitrogen atom can be replaced by C _1-3 alkyl, C _1-3 alkoxy, amino C _2-3 alkoxy, C _1-3 alkylamino C _2-3 alkoxy, di ( C _1-3 alkyl) amino-C _2-3 alkoxy-, phenyl-C _1-3 alkylamino-5 006080

C _2-3 alkoxy-, L- (C1. Zalkyl) phenyl-C1. Zalkylamino-C ₂ .zalkoxy-, iirrolidino-C ₂ . ₃ alkoxy, piperidinoC ₂ _ ₃ alkoxy or C _1-3 alkyl mercido group, carboxy group, C _1-4 alkoxycarbonyl, aminocarbonyl, C _1-3 alkylaminocarbonyl, phenyl C _1-3 alkylaminocarbonyl or Y- (C _1-3 alkyl) phenyl-C _1-3 alkylaminocarbonyl, C _3-7 cycloalkylcarbonyl, while the methylene group in position 4 of the 6- or 7-membered cycloalkyl fragment can be replaced by -ΝΗ- or -Y (C _1-3 alkyl) -, 4- 7-membered cycloalkylenimino group in which the methylene group bound to the imino group can be replaced by carbonyl or sulfonyl, or one or two hydrogen atoms in ka In this case, C _1-3 alkyl may be replaced, and / or in each case, the methylene group in position 4 of the 6- or 7-membered cycloalkylenimino group may be replaced by a carboxy group, C _1-3 alkoxycarbonyl, aminocarbonyl, C _1-3 alkylaminocarbonyl, di - (C _1-3 alkyl) aminocarbonyl, phenyl-C _1-3 alkylamino or No. (C _1-3 alkyl) phenyl-C _1-3 alkylamino or replaced by an oxygen or sulfur atom, sulfinyl, sulfonyl, -ΝΗ- or - And (C _1-3 alkyl) -, substituted in the terminal position by the group I ₇ C _1-4 alkyl, where

I ₇ means C _5-7 cycloalkyl, while the methylene group in position 4 of the 6- or 7-membered cycloalkyl group can be replaced by -ΝΗ- or -I (C _1-3 alkyl) - or in the 5-7-membered cycloalkyl group - (CH ₂ ) ₂ - group can be replaced by group -CO-ΝΗ-, group - (SI ₂ ) ₃ - can be replaced with group -ΝΗ-ί.ί--or group - (CH ₂ ) ₄ - can be replaced by the group -ΝΗ-ί.Ό-ΝΗ-ί.Ό-, and in each case the hydrogen atom bound to the nitrogen atom can be replaced by C _1-3 alkyl, phenyl or heteroaryl, hydroxy group or C _1-3 alkoxy, amino, C _1-6 alkylamino, di- (C _1-6 lkil) amino, phenylamino, №fenil-C _1-3 alkylamino, phenyl C _1-3 alkylamino, № (C _1-3 -alkyl) -phenyl-C _1-3 alkylamino or di- (phenyl-C _1-3 alkyl) amino group, w-hydroxy-C _2-3 alkylamino, No. (C _1-3 alkyl) -sh-hydroxy-C _2-3 alkylamino, di- (w-hydroxy-C _2-3 alkyl ) amino, di- (y- (C _1-3 alkoxy) -C ₂ - ₃ alkyl) amino or no. (dioxolan-2-yl) -C _1-3 alkylamino group,

C _1-3 alkylsulfonylamino-, No. (C _1-3 alkyl) -C _1-3 alkylsulfonylamino, C _1-3 alkylsulfonylamino _2-3 alkylamino or C _1-3 alkylsulfonylamino-C _2-3 alkyl-No (C _{1 -3} alkyl) amino group, hydroxycarbonyl-C _1-3 alkylamino or No. (C _1-3 alkyl) hydroxycarbonyl-C _1-3 alkylamino group, guanidino, in which a hydrogen atom can be replaced by C _1-3 alkyl, a group of the formula

-Ν (Κ ₈ ) -Ο3-№) η-Κ.9 (II), in which I ₈ represents a hydrogen atom or C _1-3 alkyl, η represents one of the numbers 0, 1, 2 or 3 and represents an amino, C _1-3 alkylamino, di (C _1-3 alkyl) amino, phenylamino, benzylamino or C _1-4 alkoxy group, a 5-7-membered cycloalkylenimino group, while the methylene group at the 4-position of the piperidine group can be replaced by an oxygen or sulfur atom, -ΝΗ-, -I (C _1-3 alkyl) -, -K (phenyl) -, -I (C _1-3 alkylcarbonyl) - or -Y (benzoyl) -, or, if η means one of the numbers 1, 2 or 3, also represents a hydrogen atom, a group of

-Ν ^ - ^ Ην ^ ΟΧ, -Κη (III), in which I ₁₀ represents a hydrogen atom, C _1-3 alkyl, C _1-3 alkylcarbonyl or C _1-3 alkylsulfonyl, t represents one of the numbers 1, 2 or 3, o is the number 1 or, if t is one of the numbers 2 or 3, is also the number 0 and

I ₁₁ is an amino, C _1-3 alkylamino, di (C _1-3 alkyl) amino, C _1-4 alkoxy or C _1-3 alkoxy-C _1-3 alkoxy group or a 5-7-membered cycloalkylenimino group, wherein the methylene group in position 4 of the piperidino group can be replaced by an oxygen or sulfur atom, -ΝΗ-, -Y (C _1-3 alkyl) -, -И (phenyl) -, -И (C _1-3 alkylcarbonyl) - or -Y (benzoyl) -,

C _4-7 cycloalkylamino or C _4-7 cycloalkenylamino group in which the position 1 of the ring does not participate in the formation of a double bond,

A 4-7-membered cycloalkylenimino group in which the cycloalkylene moiety can be condensed with a phenyl group or one or two hydrogen atoms in each case can be replaced with a C _1-3 alkyl and / or methylene group at the 3-position of the pyrrolidino group can be replaced by a hydroxy group or C1 - 3 alkoxy group, in each case, the methylene group in position 4 of the 6- or 7-membered cycloalkylamino group may be substituted by a hydroxy group, a hydroxy-C _1-3 alkyl, C _1-3 alkoxy group, a carboxy group,

C _1-3 alkoxycarbonyl, aminocarbonyl, C _1-3 alkylaminocarbonyl, di- (C _1-3 alkyl) aminocarbonyl, phenyl-C _1-3 alkylamino or No. (C _1-3 alkyl) phenyl-C _1-3 alkylamino or replaced on atom

- 6 006080 oxygen or sulfur, sulfinyl, sulfonyl, -ΝΗ-, - ^ C _1-3 alkyl) -, -Y (phenyl) -, - ^ phenyl-C _1-3 alkyl -) -, - ^ С _{1- 3} alkylcarbonyl) -, - ^ C _1-4 alkoxycarbonyl -) -, - ^ benzoyl) - or - ^ phenyl-C _1-3 alkylcarbonyl) -, while the methylene group bound to the imine nitrogen atom of the cycloalkylenimino group can be replaced by carbonyl or a sulfonyl or in a 5–6 membered monocyclic or cycloalkylamino group condensed with a phenyl group, both methylene groups bound to an imine nitrogen atom can in each case be replaced by carbonyl, or

K. ₆ means C _1-4 alkyl, which is substituted in the terminal position with a carboxy group, C _1-3 alkoxycarbonyl, aminocarbonyl, C _1-3 alkylaminocarbonyl or di (C _1-3 alkyl) aminocarbonyl or 47-membered cycloalkylenimino carbonyl group, a group of the formula

-LCH-SCH-SOTsODr-K-in (IV), in which K ₁₂ represents a hydrogen atom, C _1-3 alkyl, C _5-7 cycloalkyl, phenyl-C _1-3 alkyl or heteroaryl C _1-3 alkyl p is one of the numbers 0, 1, 2 or 3 and

K. ₁₃ takes the values of the above group K ₇ or, if p means one of the numbers 1, 2 or 3, also represents a hydrogen atom, a group of the formula

-LCH-vMSCHMSOX-KV (V), in which K ₁₄ is a hydrogen atom, C _1-4 alkyl, C _1-3 alkylcarbonyl, phenylcarbonyl, phenylC _1-3 alkylcarbonyl, heteroarylcarbonyl, heteroaryl-C _1-3 alkylcarbonyl, C _1-3 alkylsulfonyl, phenylsulfonyl, phenyl-C _1-3 alkylsulfonyl, heteroarylsulfonyl or heteroaryl-C _1-3 alkylsulfonyl,

c. | is one of the numbers 1, 2, 3, or 4, g means the number 1 or, if c. | means one of the numbers 2, 3 or 4, is also the number 0 and K ₁₅ takes the values of the above group K ₇ , a group of the formula

-Ν (Κ16) -8θ2-Κ17 (VI), in which

K. ₁₆ represents a hydrogen atom or optionally substituted at the terminal position by a cyano group, a trifluoromethylcarbonylamino group or a C1 (C _1-3 alkyl) trifluoromethylcarbonylamino group C1-4 alkyl and

K ₁₇ is C _1-3 alkyl, or is substituted di- (C _1-3 alkyl) amino-C _1-3 alkylcarbonyl or di (C1-3 alkyl) amino-C1-3 alkylsulfonyl and di- (C1-3 alkyl) S1-3alkilom aminocarbonyl-amino, all connected by a single bond or fused phenyl groups contained in these residues for R ₆ may be mono- or disubstituted by fluorine, chlorine or bromine, C _1-3 alkyl, trifluoromethyl, hydroxy, C _1-3 alkoxy group, carboxy group, C _1-3 alkoxycarbonyl, aminocarbonyl, C1-3 alkylaminocarbonyl, aminosulfonyl, C 1-3 alkyl-aminosulfonyl, nitro, or cyano groups, wherein the substituents may be identical or different, or two adjacent hydrogen atoms of the phenyl groups may be replaced by a methylenedioxy group, and

To ₅ represents a hydrogen atom or C _1-3 alkyl, wherein the heteroaryl group under the aforementioned should be understood optionally substituted in the carbon skeleton C _1-3 alkyl, pyridinyl, pyrazinyl, pyrimidinyl, pyridazinyl, pyrrolyl, furyl, thienyl, oxazolyl, thiazolyl, pyrazolyl, imidazolyl or triazolyl groups in which a hydrogen atom bound to a nitrogen atom can be replaced by a C _1-3 alkyl or phenyl C _1-3 alkyl, and 5-membered heteroaryl groups contain at least one imino group through a carbon or nitrogen atom, a hydrogen atom bound in the above residues in each case with a nitrogen atom can be replaced by a cleavable ίη νίνο residue, primarily acetyl or tert-butoxycarbonyl contained in the above carboxy group residues in each case can also be replaced detachable ίη νίνο residue and can be represented in the form of, for example, tert-butoxycarbonyl, hydrogen atoms in the above alkyl and alkoxy groups or in the alkyl fragments contained in the above for formula I groups may be partially or completely replaced by fluorine atoms and the saturated alkyl and alkoxy moieties contained in the above residues, which contain more than 2 carbon atoms, may be, unless otherwise indicated, linear or branched, their tautomers, their diastereomers, their enantiomers, their mixtures and their salts.

Among the preferred compounds of general formula I, a subgroup of compounds in which X, K ₁ and K ₃ -K ₅ have the meanings indicated above, and K ₂ means a linear or branched C _1-6 alkoxycarbonyl group, C _5-7 cycloalkoxycarbonyl or phenoxycarbonyl , linear or branched C _1-3 alkoxycarbonyl group, the alkyl fragment of which is substituted in the terminal position by phenyl, carboxy group, C _1-3 alkoxycarbonyl, aminocarbonyl, C _1-3 alkylamino-7 00 6080 carbonyl or di- (C 2 alkyl) aminocarbonyl, linear or branched hydrochloric C _2-3 alkoxycarbonyl group, the alkyl moiety is substituted at the terminal position with hydroxy, C _1-3 alkoxy, amino, C _1-3 alkylamino or di- _(C1-3 alkyl) amino group, their tautomers, their diastereomers, their enantiomers , mixtures thereof and their salts.

As the second subgroup of preferred compounds of the general formula I, it should be especially noted that compounds in which X, K ₁ and K ₃ -K ₅ have the above values, and

K ₂ means aminocarbonyl or methylaminocarbonyl, optionally substituted in position 2 of an ethyl group by a hydroxy group or a C _1-3 alkoxy group, ethylaminocarbonyl or, if K ₄ does not mean aminosulfonylphenyl or Na- (C _1-5 alkyl) -C _1-3 alkylaminocarbonylphenyl, also di- (C _1-2 alkyl) aminocarbonyl, their tautomers, their diastereomers, their enantiomers, their mixtures and their salts.

As a third subgroup of preferred compounds of general formula I, it should be particularly noted, in addition, compounds in which X, K ₁ -K ₃ and K ₅ have the above values, and

K ₄ means K ₇ - (n-C _1-4 alkyl) phenyl group, in which

K ₇ is amino, C _1-6 alkylamino, di- (C _1-6 alkyl) amino, phenylamino, L-phenyl-C _1-3 alkylamino, phenyl-C _1-3 alkylamino, X - (C _1-3 alkyl) phenyl-C _1-3 alkylamino or di (phenyl-C _1-3 alkyl) -amino group, or a phenyl group substituted by a group of the formula

-X (K12) -CO- (CH2) p-C13 (IV), in which K ₁₂ , p and K ₁₃ have the above values, their tautomers, their diastereomers, their enantiomers, their mixtures and their salts.

More preferred are compounds of the general formula I, in which X represents an oxygen atom,

K ₁ means a hydrogen atom,

K ₂ means a carboxy group, a linear or branched C _1-4 alkoxycarbonyl group or phenoxycarbonyl, a linear or branched C _1-3 alkoxycarbonyl group, the alkyl fragment of which is substituted at the terminal position with phenyl, carboxy group, C _1-3 alkoxycarbonyl, aminocarbonyl, C _1-3 alkylaminocarbonyl or di- (C _1-3 alkyl) aminocarbonyl, a linear or branched C _2-3 alkoxycarbonyl group, an alkyl moiety which is terminally substituted with a hydroxy group, a C _1-3 alkoxy group, an amino group, a C _1-3 alkylamino group oh or di- (C _1-3 alkyl) amino group, aminocarbonyl or methylaminocarbonyl, optionally substituted in position 2 of the ethyl group by a hydroxy group or C _1-3 alkoxy group of ethylaminocarbonyl or, if not means aminosulfonylphenyl or L- (C _1-5 alkyl) -C _1-3 alkylaminocarbonyl, means also di- (C _1-2 alkyl) aminocarbonyl,

K ₃ means C _1-4 alkyl or phenyl, which may be substituted by a fluorine atom, chlorine or bromine, trifluoromethyl, C _1-3 alkyl, hydroxy group or C _1-3 alkoxy group,

K ₄ means C _5-6 cycloalkyl, while the methylene group in position 4 of the cyclohexyl group may be replaced by an amino group, a C _1-3 alkylamino group or a di (C _1-3 alkyl) amino group or replaced by -ΝΗ- or -Y (C _1-3 alkyl) -, phenyl, disubstituted With _1-3 alkyl, With _1-3 alkoxygroup or phenyl nitro, the substituents may be identical or different, or substituted by the group K <5 phenyl, which may additionally be replaced by a fluorine atom, chlorine or bromine, amino or nitro, wherein K ₆ is a fluorine atom, a chlorine or bromine atom, a C _1-3 keel, C _1-3 alkoxy, nitro, amino or S5-6tsikloalkil linked through a carbon atom, pyrrolyl, pyrazolyl, imidazolyl, triazolyl or tetrazolyl group, said heteroaromatic group may be substituted in the carbon skeleton C _1-3 alkyl or associated with a nitrogen atom, a hydrogen atom can be replaced with C _1-3 alkyl or phenyl-C _1-3 alkyl, or it means a group of the formula

carboxy group, C _1-4 alkoxycarbonyl, phenyl-C _1-3 alkylaminocarbonyl or C _5-7 cycloalkylcarbonyl, 5 or 6-membered cycloalkylenymino group, with the methylene group at the 4-position of the piperidine group can be replaced by an oxygen or sulfur atom, -ΝΗ- or - ^ C _1-3 alkyl) -, unbranched, substituted in the terminal position by the group K ₇ C _1-3 alkyl, where

K ₇ means C _5-7 cycloalkyl, while in the 5- or 6-membered cycloalkyl group the group - (CH ₂ ) ₂ can be replaced by the group -CO-ΝΗ-, the group - (CH ₂ ) ₃ - can be replaced by the group -ΝΗ ^ Ο-ΝΗ- 8 006080 or the group - (CH ₂ ) ₄ - can be replaced by the group -ΝΗ-CO-ΝΗ-CO-, and in each case the hydrogen atom bound to the nitrogen atom can be replaced by C1 _{- 3} alkyl, phenyl or pyridinyl, or a pyrrolyl, pyrazolyl, imidazolyl or triazolyl group bonded via a carbon or nitrogen atom, these heteroaromatic groups being substituted in the carbon skeleton of a C _1-3 alkyl or a hydrogen atom bound to a nitrogen atom, it can be replaced by a C _1-3 alkyl, hydroxy or C _1-3 alkoxy, amino, C ₁ -alkylamino, di (C _1-3 alkyl ) amino-, phenylamino-, No. phenyl-C _1-3 alkylamino, phenyl-C _1-3 alkylamino- or No. (C _1-3 alkyl) phenyl-C _1-3 alkylamino group, w-hydroxy-C _2-3 alkylamino-, no. (C _1-3 alkyl) -sh-hydroxy-C _2-3 alkylamino, di- (y-hydroxy-C _2-3 alkyl) amino- or di- (y-c (C _1-3 alkoxy ) —C _2-3 alkyl) amino group,

C _1-3 alkylcarbonylamino-C _2-3 lkylamino or C _1-3 alkylcarbonylamino-C _2-3 alkyl-No (C _1-3 alkyl) amino group,

C _1-3 alkylsulfonylamino-, No. (C _1-3 alkyl) -C _1-3 alkylsulfonylamino, C _1-3 alkylsulfonylamino _2-3 alkylamino or C _1-3 alkylsulfonylamino-C _2-3 alkyl-No (C _{1 -3} alkyl) amino group, hydroxycarbonyl-C _1-3 alkylamino or NO (C _1-3 alkyl) hydroxycarbonyl-C _1-3 alkylamino group, guanidino, in which a hydrogen atom can be replaced by C1-3 alkyl, a group of the formula

-LCK ₈ ) -CO- (SI2) _P -K ₉ (II), in which

K ₈ represents a hydrogen atom or C _1-3 alkyl, η represents one of the numbers 0, 1, 2 or 3 and

K ₉ is an amino, C _1-3 alkylamino, di- (C _1-3 alkyl) amino or C _1-4 alkoxy group, 5- or 6-membered cycloalkylenimino group, while the methylene group in position 4 of the piperidino group can be replaced by the group -ΝΗ-, - ^ C _1-3 alkyl) - or - ^ C _1-3 alkylcarbonyl) -, or, if η means one of the numbers 1, 2 or 3, also represents a hydrogen atom, a group of the formula

-ZHKYUMSCHMSO-Kts (III), in which K ₁₀ represents a hydrogen atom or C _1-3 alkyl, t represents one of the numbers 1, 2 or 3, o represents the number 1 or, if t means one of the numbers 2 or 3 is also the number 0 and

K. n represents an amino, C _1-3 alkylamino, di- (C _1-3 alkyl) amino, C _1-4 alkoxy or methoxyC _1-3 alkoxy group or a 5- or 6-membered cycloalkylamino group, while the methylene group in position 4 of the piperidino group can be replaced by the group -ΝΗ-, - ^ C _1-3 alkyl) - or - ^ C _1-3 alkylcarbonyl) -, azetidino-, pyrrolidino-, piperidino-, 2,6-dimethylpiperidino-, 3 , 5-dimethylpiperidino- or azepino group, while the methylene group in position 3 of the pyrrolidino group can be substituted by hydroxy group, the methylene group in position 4 of the piperidino group can substituted by hydroxy, hydroxy-C1-3 alkyl or C1-3 alkoxygroup or replaced by an oxygen or sulfur atom, sulfinyl, sulfonyl, -ΝΗ-, -MS | _-3 alkyl) -. - ^ C _1-3 alkylcarbonyl) -, - ^ benzoyl) - or -Mphenyl-C _1-3 alkylcarbonyl) -, and the methylene group bound to the imine nitrogen atom of the pyrrolidino, piperidino or piperazino group may be replaced by carbonyl, or

K. ₆ means straight-chain C _1-3 alkyl, which is substituted in the terminal position with a carboxy group or C1-3 alkoxycarbonyl, a group of the formula

-BDK ₁₂ ) -CO- (CH ₂ X> -K13 (IV), in which K ₁₂ represents a hydrogen atom, C _1-3 alkyl or phenyl-C _1-3 alkyl, p represents one of 0, 1 or 2 and

K _1-3 is amino, C _1-4 alkylamino, di- (C _1-4 alkyl) amino, benzylamino, No. (C _1-3 alkyl) benzylamino, C _1-3 alkoxy-C _{1 -3} alkylamino-, No. (C _1-3 alkyl) -C _1-3 alkoxy-C _1-3 alkylamino, di- (2-methoxyethyl) amino-, di- (n-hydroxy-C _2-3 alkyl) an amino or aminocarbonylmethyl-No (methyl) amino group linked via a nitrogen atom, an optionally substituted C _1-3 alkyl pyrrolyl, pyrazolyl or imidazolyl group, a pyrrolidino, piperidino, morpholino, thiomorpholino or optionally substituted in position 4 With _{1 - 3} alkyl, phenyl-C _1-3 alkyl, C _1-3 alkylcarbonyl Is C _1-4 alkoxycarbonyl piperazino or if η is the number 1 or 2, also represents a hydrogen atom, a group of the formula

-LCMMSCHIAASOF-K ^ (V), in which

- 9 006080

By ₁₄ represents a hydrogen atom, S1_ ₄ alkyl, C1. ₃ alkylcarbonyl, phenylcarbonyl, phenyl-C1_ ₃ alkylcarbonyl, furylcarbonyl, pyridinylcarbonyl, furyl-C _1-3 alkylcarbonyl, pyridinyl-C _1-3 alkylcarbonyl, C _1-4 alkylsulfonyl, phenylsulfonyl or phenyl- _1-3 alkylsulfonyl,

c. | is one of the numbers 1, 2 or 3, g is the number 1 or, if c. | means one of the numbers 2 or 3, is also the number 0 and

K ₁₅ is amino, C _1-4 alkylamino, di- (C _1-4 alkyl) amino, phenylamino, M- (C _1-4 alkyl) phenylamino, benzylamino or N- (C _{1- 4} alkyl) benzylamino group, or a group of the formula

-Ν (Κ ₁₆ ) -8Θ2-Κ17 (VI), in which

K ₁₆ represents a hydrogen atom or optionally substituted at the terminal position by a cyano group, a trifluoromethylcarbonylamino group or a No. (C _1-3 alkyl) trifluoromethylcarbonylamino group With a _1-3 alkyl and

C ₁₇ is C _1-3 alkyl, with all the simple bonded or fused phenyl groups contained in the residues indicated for K ₆ may be replaced by a fluorine, chlorine or bromine atom, methyl, trifluoromethyl, methoxy, nitro or cyano, and

To ₅ means a hydrogen atom, while the hydrogen atom, which in the above residues in each case is linked to the nitrogen atom, can be replaced by acetyl or tert-butoxycarbonyl contained in the above residues of the carboxy group, can also be present as a tert-butoxycarbonyl group - the precursor and the saturated alkyl and alkoxy fragments contained in the above residues, which contain more than 2 carbon atoms, may be, unless otherwise specified, linear or branched, their tautomers, their diastereomers, their en ntiomery, mixtures thereof and the salts thereof.

Among the more preferred compounds of general formula I, a particular subgroup of compounds in which X, K ₁ , K ₃ and K ₅ are as defined above should be singled out,

K ₂ means a linear or branched C _1-4 alkoxycarbonyl group or a phenoxycarbonyl, a linear or branched C _1-3 alkoxycarbonyl group, the alkyl fragment of which is substituted at the terminal position with a phenyl, carboxy group, C _1-3 alkoxycarbonyl, aminocarbonyl, C _1-3 alkylaminocarbonyl or di (C1-3alkyl) aminocarbonyl, or a linear or branched S2-3alkoksikarbonilnuyu group, the alkyl moiety is substituted at the terminal position with hydroxy, C _1-3 alkoxy, amino, C _1-3 alkylamino or di- (C _1-3 and kil) amino group, and

K ₄ means K ₇ - (n-C _1-3 alkyl) phenyl group in which

K ₇ is amino, C _1-6 alkylamino, di- (C _1-4 alkyl) amino, w-hydroxy-C _2-3 alkylamino, n (C _1-3 alkyl) -sh-hydroxy- C _2-3 alkylamino, di- (w-hydroxy-C _2-3 alkyl) amino or di (w- (C _1-3 alkoxy) -C _2-3 alkyl) amino group, or a phenyl group substituted by a group formulas

-VDad-CO-SODr-Kp (IV), in which K ₁₂ , p and K ₁₃ have the above values, their tautomers, their diastereomers, their enantiomers, their mixtures and their salts.

As the second subgroup of more preferred compounds of general formula I, special mention should be made of compounds in which X, K ₁ , K ₃ and K ₅ have the above values,

K ₂ is aminocarbonyl or methylaminocarbonyl, optionally substituted in position 2 of an ethyl group by a hydroxy group or a C _1-3 alkoxy group of ethylaminocarbonyl, or, if K ₄ does not mean aminosulfonylphenyl or C (No. _1-5 alkyl) -C _1-3 alkylaminocarbonyl, (C _1-2 alkyl) aminocarbonyl and

K ₄ means K ₇ - (n-C _1-3 alkyl) phenyl group in which

K ₇ is amino, C _1-6 alkylamino, di- (C _1-4 alkyl) amino, w-hydroxy-C _2-3 alkylamino, n (C _1-3 alkyl) -sh-hydroxy- C _2-3 alkylamino, di- (y-hydroxy-C _2-3 alkyl) amino or di- (y- (C _1-3 alkoxy) -C _2-3 alkyl) amino group, or a phenyl group substituted by a group formulas

-BDC ₁₂ ) -CO- (CH ₂ ) p-C13 (IV), in which K ₁₂ , p and K ₁₃ have the above values, their tautomers, their diastereomers, their enantiomers, their mixtures and their salts.

Most preferred are compounds of the general formula I, wherein

X means an oxygen atom

K ₁ and K ₅ each means a hydrogen atom,

K ₂ means methoxycarbonyl, ethoxycarbonyl or aminocarbonyl,

K ₃ means phenyl and

K ₄ means monosubstituted by the group K ₆ phenyl, where

K ₆ means No. methylimidazol-2-yl,

- 10 006080 ₃ S1_ unbranched alkyl which is substituted in the terminal position with C1 _-4 alkylamino, di (S1.4alkil) amino, piperidino or 2,6-dimetilpiperidinogruppoy, a group of formula

M (K12) -CO- (CH2) p-K1z (IV), in which

K ₁₂ is C _1-3 alkyl, p is one of the numbers 1 or 2, and

K _1-3 represents a di- (C _1-3 alkyl) amino group or a group of the formula

-M (K14) - (CH2) _H - (CO) _G -K15 (V), in which

K ₁₄ is C _1-3 alkylcarbonyl or C _1-3 alkylsulfonyl,

K ₁₅ is a di- (C _1-3 alkyl) amino group, while the saturated alkyl fragments contained in the above residues, which contain more than 2 carbon atoms, may be, unless otherwise indicated, linear or branched, their tautomers, their diastereomers , their enantiomers, their mixtures and their salts.

Among the most preferred compounds of general formula I, particular mention should be made of compounds in which X, K ₁ , K ₃ and K ₅ are as defined above,

K ₂ means methoxycarbonyl or ethoxycarbonyl and

To ₄ means di- (C _1-3 alkyl) amino-C _1-3 alkylphenyl or a phenyl group substituted by a group of the formula

As particularly preferred compounds, the following should be mentioned in the first place:

(a) 3-Ζ- [1- (4- (piperidin-1 -ylmethyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (b) 3 ^ - [(1- (4- ( piperidin-1-methyl) anilino) -1-phenylmethylene] -6-carbamoyl-2-indolinone, (c) 3-Ζ- [1 - (4- (piperidin-1-methylmethyl) anilino) -1-phenylmethylene] - 6-methoxycarbonyl-2-indolinone, (g) 3 ^ - [1- (4- (dimethylaminomethyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (e) 3-Ζ- [1 - ( 4 - ((2,6-dimethylpiperidin-1-yl) methyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2indolinone, (e) 3 -Ζ- [1 - (4- (X- (2-dimethylaminoethyl ) -Y-acetylamino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (g) 3 -Ζ- [1 - (4- (Ν- (3-dimethylamine propyl) -Y-acetylamino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (h) 3 ^ - [1- (4- (No. (2-dimethylaminoethyl) -Nmethylsulfonylamino) anilino) -1 -phenylmethylene] -6ethoxycarbonyl-2-indolinone, (and) 3 ^ - [1- (4- (dimethylaminomethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone, (k) 3 -Ζ- [1 - (4- (no. Acetyl-dimethylaminocarbonylmethylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone, (l) 3-Ζ- [1 - (4-ethylaminomethylanilino) -1-phenylmethylene] -6- methoxycarbonyl-2-indolinone, (m) 3 -Ζ- [1 - (4- (1-methylimidazol-2-yl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone, (n) 3 -Ζ - [1- (4- ( No. dimethylaminomethylcarbonyl-No. methylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone, (o) 3 -Ζ- [1 - (4- (no. (2-dimethylaminoethyl) -№methylsulfonylamino) anilino) -1 -phenylmethylene] -6methoxycarbonyl-2-indolinone, (p) 3 -Ζ- [1 - (4- (Ν- (3-dimethylaminopropyl) -Nomethylsulfonylamino) anilino) -1-phenylmethylene] -6methoxycarbonyl-2-indolinone, ( p) 3 -Ζ- [1 - (4- (No. dimethylaminocarbonylmethyl-No. methylsulfonylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone, (c) 3 -Ζ- [1 - (4- ( ((2-dimethylaminoethyl) carbonyl) -Nomethylamino) anilino) -1-phenylmethylene] -6methoxycarbonyl-2-indolinone, (t) 3 -Ζ- [1- (4- (No. (2-dimethylaminoethyl) -Noacetylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone and (y) 3-Ζ- [1- (4- Methylaminomethylanilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone, their tautomers, mixtures thereof, and their salts.

As another subgroup of compounds of the general formula I, there should be mentioned compounds in which

X means an oxygen or sulfur atom,

- 11 006080

AT! means a hydrogen atom or a prodrug residue, such as

C1. ₄ alkoxycarbonyl or C _2-4 alkanoyl,

B ₂ means a carboxy group, a linear or branched C _1-6 alkoxycarbonyl group, C5.7 cycloalkoxycarbonyl or phenyl-C ₁ _ ₃ alkoxycarbonyl, aminocarbonyl or C ₁ _ ₂ alkylaminocarbonyl or, if B ₄ does not mean aminosulfonylphenyl or L- (C _{1- 5} alkyl) -C _1-3 carbonylaminocarbonyl, also means di- (C _1-2 alkyl) aminocarbonyl,

B ₃ means a hydrogen atom, C _1-6 alkyl, C _3-7 cycloalkyl, trifluoromethyl or heteroaryl, phenyl or naphthyl, mono- or disubstituted with a fluorine atom, chlorine, bromine or iodine, trifluoromethyl, C _1-3 alkyl or C _{1- 3} alkoxygroup phenyl or naphthyl, while in the case of substitution by two groups, the substituents can be identical or different, and the above unsubstituted, as well as mono- and disubstituted phenyl and naphthyl groups can additionally be replaced by hydroxy group, hydroxy-C _1-3 alkyl or C _{1 -3} alkoxy- _1-3 alkyl, cyano, carboxygroup oh, carboxy-C _1-3 alkyl, C _1-3 alkoxycarbonyl, aminocarbonyl, C _1-3 alkylaminocarbonyl or di- (C _1-3 alkyl) aminocarbonyl, nitro, amino, C _1-3 alkylamino, di- (C _{1 -3} alkyl) amino or amino-C _1-3 alkyl,

C _1-3 alkylcarbonylamino, N- (C _1-3 alkyl) -C _1-3 alkylcarbonylamino, C _1-3 alkylcarbonylamino-C _1-3 alkyl, N- (C _1-3 alkyl) -C _1-3 alkylcarbonylamino C _1-3 alkyl, C _1-3 alkylsulfonylamino, C _1-3 alkylsulfonylamino-C _1-3 alkyl, N- (C _1-3 alkyl) -C _1-3 alkylsulfonylamino-C _1-3 alkyl or aryl-C1- 3 alkylsulfonylamino, cycloalkylamino, cycloalkylenimino, cycloalkyleniminocarbonyl, cycloalkylenimino-C _1-3 alkyl, cycloalkyleniminocarbonyl-C _1-3 alkyl or cycloalkylenimino sulfonylC1-3 alkyl in each case with 4-7 rings primes, in which case the methylene group in each case in position 4 in a 6- or 7-membered cycloalkylenimino group can be replaced by an oxygen or sulfur atom, sulfinyl, sulfonyl, -ΝΗ- or -Y (C _1-3 alkyl) -, or heteroaryl or heteroaryl-C _1-3 alkyl,

B4 means C3-7cycloalkyl, wherein the methylene group in position 4 of the 6- or 7-membered cycloalkyl group may be substituted by an amino group, a C _1-3 alkylamino group or a di- (C _1-3 alkyl) amino group or replaced by -ΝΗ or -MS | _-3 alkyl) -. or substituted by group B ₆ phenyl, which may additionally be substituted by a fluorine atom, chlorine, bromine or iodine, C _1-5 alkyl, trifluoromethyl, C _1-3 alkoxy group, carboxy group, C _1-3 alkoxycarbonyl, aminosulfonyl, nitro group or cyano group, with by this

In ₆ means a hydrogen atom, fluorine, chlorine, bromine or iodine, cyano, nitro, C _1-5 alkyl, C _3-7 cycloalkyl, trifluoromethyl, phenyl, tetrazolyl or heteroaryl, optionally substituted with 1-3 fluorine atoms With _1-3 alkoxy or C _1-3 alkoxy-C _1-3 alkoxy-, phenyl-C _1-3 alkoxy-, amino-C _2-3 alkoxy-, C _1-3 alkylamino-C _2-3 alkoxy-, di- (C _{1 -3} alkyl) amino-C _2-3 alkoxy-, phenyl-C _1-3 alkylamino-C _2-3 alkoxy-, No. (C _1-3 alkyl) phenyl-C1-3 alkylamino-C2-3 alkoxy-, C5-7cycloalkylenimino -C2-3 alkoxy- or C1-3 alkyl mercapto group, carboxy group, C _1-4 alkoxycarbonyl, aminocarbonyl, C _1-3 alk Ilaminocarbonyl, No. (C _1-5 alkyl) C _1-3 alkyl aminocarbonyl, phenyl-C _1-3 alkylaminocarbonyl, No. (C _1-3 alkyl) phenyl-C _1-3 alkylaminocarbonyl, piperazinocarbonyl or No. (C _1-3 alkyl ) piperazinocarbonyl, C _1-3 alkylaminocarbonyl or No. (C _1-5 alkyl) C _1-3 alkylaminocarbonyl in which the alkyl fragment is substituted by carboxy group or C _1-3 alkoxycarbonyl or in position 2 or 3 is replaced by di- (C _1-3 alkyl a) an amino group, a piperazino group, no. (C _1-3 alkyl) piperazino group or a 4-7-membered cycloalkylenimino group, a 4-7-membered cycloalkylenimino group in which it is associated with iminogram A methylene group can be replaced by a carbonyl or sulfonyl or a cycloalkylene moiety can be condensed with a phenyl ring or one or two hydrogen atoms in each case can be replaced with a C _1-3 alkyl and / or methylene group in each case in position 4 6- or a 7-membered cycloalkylamino group may be substituted by a carboxy group, C _1-3 alkoxycarbonyl, aminocarbonyl, C _1-3 alkylaminocarbonyl, di- (C _1-3 alkyl) aminocarbonyl, phenyl-C _1-3 alkylamino or NO (C _1-3 alkyl ) alkylamino or phenylC _1-3 substituting on an oxygen atom or sulfur atom, sulfinyl, sulfonyl, -ΝΗ-, -Ν (Οι_ ₃ alkyl) -, -№ (phenyl) -, - ^ C _1-3 -alkylcarbonyl) - or ^ (benzoyl) -, C _{1- 4} alkyl, which is substituted by a hydroxy group or a C1-3 alkoxy group, an amino group, a C _1-7 alkylamino group, a di (C _1-7 alkyl) amino group, a di-no. (C _1-3 alkyl) amino C _2-3 alkylamino group, a tri- ^^ No.- (C _1-3 alkyl) amino-C _2-3 alkylamino, phenylamino, Ν phenyl-C _1-3 alkylamino, phenyl-C _1-3 alkylamino, no. (C _1-3 alkyl) phenyl-C _{1- 3} alkylamino or di- (phenyl-C1-3 alkyl) amino group,

C _1-3 alkylcarbonylamino, No. (C _1-3 alkyl) -C _1-3 alkylcarbonylamino, C _1-3 alkoxycarbonyl-C _1-3 alkylamino or No. (C _1-3 alkyl) -C _1-3 alkoxycarbonyl-C _{1 -3} alkylamino,

C _4-7 cycloalkylamino, C _4-7 cycloalkyl-C _1-3 alkylamino or C _4-7 cycloalkenylamino group, in which the position of the 1 ring does not participate in the formation of a double bond, each of the above groups may additionally be substituted at the amine atom nitrogen With _1-3 alkyl, in which the atoms of water are partially or completely replaced by fluorine atoms, C5. ₇ cycloalkyl, C _2-4 alkenyl or S1_ ₄ alkyl,

A 4-7 membered cycloalkylenimino group in which the methylene group bound to the imino group can be replaced with a carbonyl or sulfonyl or cycloalkylene moiety can be condensed with phenyl or with an optionally substituted fluorine, chlorine, bromine or iodine atom, a nitro group, C _1-3 alkyl, With _1-3 alkoxy group or amino group of oxazolo, imidazolo, thiazolo, pyridino, pyrazino or pyrimidine, or one or two hydrogen atoms in each case can be replaced by C _1-3 alkyl, C _5-7 cycloalkyl or phenyl, and / or methylene group in azhdom case in the 4 position 6- or 7-membered tsikloalkileniminogruppy may be substituted by hydroxy, carboxy, S1-4alkoksikarbonilom, aminocarbonyl, C _1-3 alkylaminocarbonyl, di (C _1-3 alkyl) aminocarbonyl, phenyl-C _1-3 alkylamino group or M- (C _1-3 alkyl) phenyl-C _1-3 alkylamino or replaced by an oxygen or sulfur atom, sulfinyl, sulfonyl, -ΝΗ-, -Y (C _1-3 alkyl) -, -Y (phenyl) -, -Y (C _1-3 alkylcarbonyl) - or -Y (benzoyl) -, carboxy, C _1-3 alkoxycarbonyl, aminocarbonyl, C _1-3 alkylaminocarbonyl or di (C _1-3 alkyl) aminocarbonyl or

4-7-membered cycloalkyleniminocarbonyl, amino, pyrrolidino, piperidino, morpholino, benzoylamino or NO (C _1-3 alkyl) benzoylamino group, NO (C _1-3 alkyl) -C _2-4 alkanoylamino, which in the alkyl the fragment is additionally substituted by a carboxy group or C1-3 alkoxycarbonyl, a group of the formula

-LCH ₈ ) -CO- (CH2) p-B9 (II), in which

B ₈ represents a hydrogen atom or C _1-3 alkyl, η means one of the numbers 0, 1, 2 or 3 and

B ₉ is amino, C _1-4 alkylamino, phenylamino, No. (C _1-4 alkyl) phenylamino, benzylamino, No. (C _1-4 alkyl) benzylamino or di (C _1-4 alkyl a) an amino group, a 4-7-membered cycloalkylenimino group, and the methylene group in each case in the 4 position of the 6- or 7-membered cycloalkylenimino group can be replaced by an oxygen or sulfur atom, sulfinyl, sulfonyl, -ΝΗ-, -Ν (Οι_ ₃ alkyl ) -, - ^ phenyl) -, ^ C _1-3 alkylcarbonyl) - or - ^ benzoyl) -, or, if η means one of the numbers 1, 2 or 3, also represents a hydrogen atom, a group of the formula ^ (VyuSNMSO ^ -Vts (iii) in which

B ₁₀ represents a hydrogen atom, C _1-3 alkyl, C _1-3 alkylcarbonyl, arylcarbonyl, phenyl-C _1-3 alkylcarbonyl, C _1-3 alkylsulfonyl, arylsulfonyl or phenyl-C _1-3 alkylsulfonyl, t means one of the numbers 1, 2, 3, or 4, o means one of the numbers 0 or 1, and

In _n represents amino, C _1-4 alkylamino, phenylamino, No. (C _1-4 alkyl) phenylamino, benzylamino, No. (C _1-4 alkyl) benzylamino or di (C _1-4 alkyl a) an amino group, a 4-7-membered cycloalkylenimino group, wherein the cycloalkylene moiety can be condensed with a phenyl ring or the methylene group in each case in position 4 of the 6- or 7-membered cycloalkylene amino group can be replaced by an oxygen or sulfur atom, sulfinyl, sulfonyl, -ΝΗ-, - ^ C _1-3 alkyl) -, - ^ phenyl) -, - ^ C _1-3 alkylcarbonyl) - or - ^ benzoyl) -, or represents a C _1-3 alkoxy group or neo optionally substituted in position 1 C _{1-3 by} alkyl di- (C _1-4 alkyl) amino-C _1-3 alkylamino group, or No. (C _1-3 alkyl) C _1-5 alkylsulfonylamino or number (C _1-3 alkyl a) a phenylsulfonylamino group in which the alkyl fragment is additionally substituted with a cyano or carboxy group, while all connected by a single bond or condensed phenyl groups contained in the B ₆ residues indicated can be mono- or disubstituted with a fluorine, chlorine, bromine or iodine atom, C _{1 -5} alkyl, trifluoromethyl, C _1-3 alkoxy, carboxy, C _1-3 alkoxycarbonyl, aminosulf Neal, nitro or cyano, where the substituents may be identical or different, or two adjacent hydrogen atoms of the phenyl groups may be replaced by a methylenedioxy group, and

B ₅ means a hydrogen atom or a C _1-3 alkyl, wherein by aryl or aryl group is meant optionally mono- or disubstituted with a fluorine, chlorine, bromine or iodine atom, trifluoromethyl, a C _1-3 alkyl or C _1-3 alkoxy group of phenyl or naphthyl a group, and a heteroaryl or heteroaryl group means a monocyclic 5-or 6-membered heteroaryl group optionally substituted with a C1-3 alkyl; the 6-membered heteroaryl group contains one, two or three nitrogen atoms, and the 5-membered heteroaryl group contains an optionally substituted C _1-3 alkyl imino group, an oxygen or sulfur atom or an optionally substituted C _1-3 alkyl imino group and an oxygen or sulfur atom or one or two nitrogen atoms, and with the above monocyclic heterocyclic groups, in addition, can be condensed through two adjacent atoms carbon phenyl ring, to the saturated alkyl and alkoxy moieties in the above groups that contain more than 2 carbon atoms,

- 13 006080 also include, unless otherwise indicated, their branched isomers, such as, for example, isopropyl, tert-butyl, isobutyl, and the carboxy, amino, or imino group present may additionally be replaced by the cleavable ίη νίνο residue, their isomers and their salts.

New compounds are prepared according to the invention, for example, by the following methods, which are known in principle from the literature.

but). In this embodiment, the compound of the general formula

wherein

X and From have the above values

K ₂ ′ is as defined above for K ₂ ,

K ₁₈ means a hydrogen atom or a protective group for the nitrogen atom of the lactam group, wherein one of the residues K ₂ ′ and K ₁₈ may also be a bond with the solid phase, optionally formed by a spacer, and the other of the residues K ₂ ′ and K ₁₈ has the above values and

Ζ ₁ means a halogen atom, a hydroxy, alkoxy or arylalkoxy group, for example a chlorine or bromine atom, a methoxy, ethoxy or benzyloxy group, is reacted with an amine of the general formula / ^K5

Η - Ν (VIII), in which K ₄ and K ₅ have the above values, and then, if necessary, remove the protective group used for the nitrogen atom of the lactam group or the compound thus obtained is cleaved from the solid phase.

As an example of a protecting group for the nitrogen atom of a lactam group, an acetyl, benzoyl, ethoxycarbonyl, tert-butyloxycarbonyl or benzyloxycarbonyl group can be mentioned, and an example of a solid phase can be called a resin such as 4- (2 ', 4-dimethoxyphenylaminomethyl) phenoxy resin, the bond is predominantly formed by the amino group, or a resin in the form of p-benzyloxybenzyl alcohol, where the bond is predominantly formed by an intermediate member, such as a 2,5-dimethoxy-4-hydroxybenzyl derivative.

The interaction described above should be carried out in a solvent such as dimethylformamide, toluene, acetonitrile, tetrahydrofuran, dimethyl sulfoxide, methylene chloride or their mixture, optionally in the presence of an inert base, such as triethylamine, Ν-ethyl diisopropylamine or sodium bicarbonate, at a temperature of from 20 to 175 ° C , at the same time as a result of reamidation at the same time splitting of the used protecting group can occur.

If in the compound of general formula VII Ζ ₁ means a halogen atom, then in this case the interaction is preferably carried out in the presence of an inert base at a temperature of from 20 to 120 ° C.

If in a compound of general formula VII, Ζ ₁ means a hydroxy, alkoxy, or arylalkoxy group, then in this case the reaction is preferably carried out at a temperature of from 20 to 200 ° C.

Necessary under certain conditions, the subsequent cleavage of the protective group used is advisable to carry out either hydrolytically in an aqueous or alcoholic solvent, for example in methanol / water, ethanol / water, isopropanol / water, tetrahydrofuran / water, dioxane / water, dimethylformamide / water, methanol or ethanol, in the presence of an alkaline base, such as lithium hydroxide, sodium hydroxide or potassium hydroxide, at a temperature of from 0 to 100 ° C, preferably from 10 to 50 ° C, or, preferably, by reamidation with an organic base such as ammonia, butylamine, dimethylamine or piperidine in a solvent such as methanol, ethanol, dimethylformamide and mixtures thereof or in an excess amount of the amine used at a temperature of 0 to 100 ° C, preferably from 10 to 50 ° C.

Cleavage from the used solid phase is preferably carried out with trifluoroacetic acid and water at a temperature of from 0 to 3 ° C, preferably at room temperature.

b). In this embodiment, to obtain a compound of general formula I, in which K ₂ is as defined above, with the exception of the carboxy group, the compound of general formula

- 14 006080

in which E and K ₃ -K ₅ have the above values, or its reactive derivatives are subjected to interaction with the compound of the general formula

HI ₁₉ (x) in which

K. | ₉ means C _1-6 alkanol, C _4-7 cycloalkanol or aromatic alcohol,

C _1-6 alkanol, the alkyl fragment of which is substituted at the terminal position by phenyl, heteroaryl, carboxy, C _1-3 alkoxycarbonyl, aminocarbonyl, C _1-3 alkylaminocarbonyl or di (C _1-3 alkyl) aminocarbonyl, C _2-6 alkanol, alkyl a fragment of which is substituted in the terminal position with a chlorine atom or a hydroxy, C _1-3 alkoxy, amino, C _1-3 alkylamino or di (C _1-3 alkyl) amino group, an amino or methylamino group, optionally substituted in the position 2 ethyl groups with a hydroxy or C _1-3 alkoxy group of an ethylamino group or a di (C _1-2 alkyl) amino group.

Esterification or amidation is preferably carried out in a solvent such as methylene chloride, diethyl ether, tetrahydrofuran, toluene, dioxane, acetonitrile, dimethyl sulfoxide or dimethylformamide, optionally in the presence of an inorganic or tertiary organic base, preferably at a temperature of from 20 ° C to the boiling point of the solvent used. The interaction with the appropriate acid is preferably carried out in the presence of a dehydrating agent, e.g. in the presence of isobutyl chloroformate, tetraethyl orthocarbonate acid, trimethyl orthoacetate, 2,2dimetoksipropana, tetramethoxysilane, thionyl chloride, trimethylchlorosilane, phosphorus trichloride, phosphorus pentoxide, Ν, Ν '-dicyclohexylcarbodiimide, X, X'-dicyclohexylcarbodiimide / X-hydroxysuccinimide, ^ N-dicyclohexylcarbodiimide / 1-hydroxybenzotriazole, tetrafluorob Orat 2- (1Nbenzotriazol-1 -yl) - 1,1,3,3-tetramethyluronium, tetrafluoroborate 2- (1H-benzotriazol-1-yl) -1,1,3,3 tetramethyluronium / 1-hydroxybenzotriazole,, '-carbonyldiimidazole or triphenylphosphine / carbon tetrachloride, and optionally with the addition of a base, such as pyridine, 4-dimethylaminopyridine, α-methylmorpholine or triethylamine, preferably at a temperature of from 0 to 150 ° C, preferably from 0 to 100 ° C, and acylation with an appropriate reactive compound such as its anhydride, ether, imidazolide or acid halide, optionally in the presence of a tertiary organic base, such as triethylamine, эти-ethyldiisopropylamine or орф methylmorpholine, at a temperature of from 0 to 150 ° C, preferably from 50 to 100 ° C.

at). In this embodiment, to obtain a compound of general formula I, in which is substituted with a K ₇ group With _1-4 alkyl, where

K ₇ means amino-, C _1-7 alkylamino, di- (C _1-7 alkyl) amino, phenylamino, No. phenyl-C _1-3 alkylamino, phenyl-C _1-3 alkylamino, no. (C _1-3 alkyl) phenyl-C _1-3 alkylamino or di (phenyl-C _1-3 alkyl) amino group, w-hydroxy-C _2-3 alkylamino, No. (C _1-3 alkyl) -sh-hydroxy -C _2-3 alkylamino-, di- (w-hydroxy-C _2-3 alkyl) amino-, di- (si- (C _1-3 alkoxy) -C _2-3 alkyl) amino- or No. (dioxolane 2-yl) -C _1-3 alkylamino,

C _1-3 alkylcarbonylamino-C _2-3 alkylamino or C _1-3 alkylcarbonylamino-C _2-3 alkyl-H- (C _1-3 alkyl) amino group,

C _1-3 alkylsulfonylamino-, No. (C _1-3 alkyl) -C _1-3 alkylsulfonylamino, C _1-3 alkylsulfonylamino _2-3 alkylamino or C _1-3 alkylsulfonylamino-C _2-3 alkyl-H- (C _1-3 alkyl) amino group, a group of the formula ^ (KyUNSNMSOXgKn (III), in which

K ₁₀ is a hydrogen atom, C _1-3 alkyl, C _1-3 alkylcarbonyl, arylcarbonyl, phenyl-C _1-3 alkylcarbonyl, C _1-3 alkylsulfonyl, arylsulfonyl or phenyl-C _1-3 alkylsulfonyl, t means one of the numbers 1, 2, 3, or 4, o means the number 1 and

K ₁₁ is amino, C _1-4 alkylamino, di- (C _1-4 alkyl) amino, phenylamino, No. (C _1-4 alkyl) phenylamino, benzylamino, No. (C _1-4 alkyl ) benzylamino, C _1-4 alkoxy, C _1-3 alkoxy-C _1-3 alkoxy group, optionally substituted in position 1 by C _1-3 alkyl by di- (C _1-4 alkyl) amino C _1-3 alkylamino group or

A 4-7-membered cycloalkylenimino group, wherein the cycloalkylene moiety may be condensed with a phenyl ring, or in each case the methylene group in position 4 of the 6- or 7-membered cycloalkylenimino group may be replaced by an oxygen or sulfur atom, sulfinyl, sulfonyl,

-ΝΗ-, -Y (C _1-3 alkyl) -, -I (phenyl) -, -I (C _1-3 alkylcarbonyl) - or -Y (benzoyl) -,

- 15 006080

C _4-7 cycloalkylamino, C _4-7 cycloalkyl-C _1-3 alkylamino or C _4-7 cycloalkenylamino group in which the position 1 of the ring does not participate in the formation of a double bond, while the above groups can additionally be substituted in each case at the amino nitrogen atom with C 5-7 cycloalkyl, C 2-4 alkenyl or C _1-4 alkyl, or

4-7-membered cycloalkylamino group in which the cycloalkylene moiety can be condensed with a phenyl group or with an oxazolo, imidazolo, thiazole, pyridino, pyrazino or pyrimidine group, optionally substituted by a fluorine atom, chlorine, bromine or iodine, nitro group, C1 -3 alkyl, C _1-3 alkoxy group or amino group, and / or one or two hydrogen atoms in each case can be replaced by C _1-3 alkyl, C _5-7 cycloalkyl or phenyl and / or methylene group in position 3 5- the cycloalkenyl-amino group may be substituted by a hydroxy group, hydroxy-C _1-3 alkyl, C1-3 alkoxy group or C1-3 alkoxy-C1-3 alkyl, in each case the methylene group in position 3 or 4 of the 6- or 7-membered cycloalkylenimino group can be replaced by hydroxy, hydroxyC _1-3 alkyl, C _{1 -3} alkoxy, C _1-3 alkoxy-C _1-3 alkyl, C _1-4 alkoxycarbonyl, aminocarbonyl, C _1-3 alkylaminocarbonyl, di- (C _1-3 alkyl) aminocarbonyl, phenyl-C _1-3 alkylamino group or (C _1-3 alkyl) phenyl-C _1-3 alkylamino or replaced by an oxygen or sulfur atom, sulfinyl, sulfonyl, -ΝΗ-, -MS _1-3 alkyl -) -. -H (phenyl) -, -Mphenyl-C _1-3 alkyl -) -. -And (C _1-3 alkylcarbonyl -) -, -I (C _1-4 alkoxycarbonyl -) -, -Y (benzoyl -) - or -Y (phenyl-C _1-3 alkylcarbonyl -) -, and associated with imino the nitrogen atom of the cycloalkylenimino group of the methylene group can be replaced by carbonyl or sulfonyl or in a 5-7-membered monocyclic or cycloalkylenimino group condensed with a phenyl group, both of the methylene groups bound to the imine nitrogen atom can be replaced in each case by carbonyl, a compound of the general formula

wherein

K ₃ , K ₅ and X are as defined above,

K ₂ ′ is as defined above for K ₂ ,

K ₁₈ means a hydrogen atom or a protective group for the nitrogen atom of the lactam group, wherein one of the residues K ₂ ′ and K ₁₈ may also be a bond with the solid phase, optionally formed by a spacer, and the other of the residues K ₂ ′ and K ₁₈ has the above values ,

A means C _1-4 alkyl and

Ζ ₂ means a leaving group, for example an alkyl or arylsulfonyloxy group such as methylsulfonyloxy, ethylsulfonyloxy, p-toluenesulfonyloxy or trifluoromethanesulfonyloxy, is reacted with an amine of the general formula

H-K _g (XII), in which K ₇ 'is as defined above for K ₇ , and then, if necessary, remove the protective group used for the nitrogen atom of the lactam group or the compound thus obtained from the solid phase.

Such a reaction is expediently carried out in a solvent such as methylene chloride, tetrahydrofuran, 1,4-dioxane, toluene, acetonitrile, dimethyl sulfoxide, dimethylformamide, dimethylacetamide, Ν-methylpyrrolidone, or mixtures thereof, optionally with water as a cosolvent and / or added bases, for example sodium bicarbonate, pyridine, 2,4,6-trimethylpyridine, quinoline, triethylamine, α-ethyldiisopropylamine, α-ethyldicyclohexylamine, 1,4-diazabicyclo [2.2.2] octane or 1,8-diazabicyclo [5, 4.0] undec-7-ene, at a temperature of from -50 to + 100 ° C, preferably from -10 to + 50 ° C, while as a result of reamidation, the protective group used can be removed simultaneously.

Necessary under certain conditions, the subsequent removal of the used protective group for the nitrogen atom of the lactam group or cleavage from the solid phase is carried out as described above for option a) method.

If, according to the invention, a compound of general formula I is obtained containing an alkoxycarbonyl group, this compound can be converted by hydrolysis to the corresponding carboxy compound, or if a compound of general formula I is obtained containing an amino or alkylamino group, then this compound can be converted by reductive alkylation to the corresponding alkylamino or a dialkylamino compound, or if a compound of the general formula I is obtained containing an amino or alkylamino group, then this compound can be translated by aci or sulfonylation into the corresponding acyl or sulfonyl compound, or if the compound is prepared

- 16 006080 of general formula I, containing a carboxy group, such a compound can be converted by esterification or amidation into the corresponding ester or the corresponding aminocarbonyl compound, or if a compound of general formula I is obtained containing a cycloalkylenimino group in which the methylene group is replaced by a sulfur atom, then this the compound can be converted by oxidation to the corresponding sulfinyl or sulfonyl compound, or if a compound of general formula I is obtained containing a nitro group, then these are compounds can be transferred by reduction to the corresponding amino compound, or if you get a compound of the general formula I, in which K4 is a substituted amino group, an alkylamino group, an aminoalkyl or alkylamino group, phenyl, then this compound can be converted by a subsequent reaction with the corresponding cyanate, isocyanate or carbamoyl halide to the corresponding urea compound of general formula I, or if a compound of general formula I is prepared, in which K ₄ is substituted by an amino group, alkyl lamino group, aminoalkyl or алки-alkylamino group phenyl, then this compound can be converted by subsequent reaction with the corresponding amidino group or by reaction with the corresponding nitrile into the corresponding guanidine compound of general formula I.

Subsequent hydrolysis is preferably carried out in an aqueous solvent, for example in water, methanol / water, ethanol / water, isopropanol / water, tetrahydrofuran / water or dioxane / water, in the presence of an acid, such as trifluoroacetic acid, hydrochloric acid or sulfuric acid, or in the presence of alkaline base, such as lithium hydroxide, sodium hydroxide or potassium hydroxide, at a temperature of from 0 to 100 ° C, preferably from 10 to 50 ° C.

Subsequent reductive alkylation is preferably carried out in a solvent suitable for this purpose, such as methanol, methanol / water, methanol / water / ammonia, ethanol, ether, tetrahydrofuran, dioxane or dimethylformamide, optionally with an acid, such as hydrochloric acid, in the presence of a catalytic activated hydrogen, for example hydrogen in the presence of Raney nickel, platinum or palladium on carbon, or in the presence of a metal hydride such as sodium borohydride, lithium borohydride, sodium cyanoborohydride or alum lithium ohydride, at a temperature of from 0 to 100 ° C, preferably from 20 to 80 ° C.

Subsequent acylation or sulfonylation is expediently carried out using an appropriate free acid or an appropriate reactive compound, such as its anhydride, or ether, imidazolide or acid halide, preferably in a solvent such as methylene chloride, diethyl ether, tetrahydrofuran, toluene, dioxane, acetonitrile, dimethyl sulfoxide or ethyl dichloride, or tetrahydrofuran, toluene, dioxane, acetonitrile, dimethyl sulfoxide or ethyl dichloride. optionally in the presence of an inorganic or tertiary organic base at a temperature of from -20 to 200 ° C, preferably from 20 ° C to the boiling point of the solvent used. The reaction with the free acid can optionally be carried out in the presence of an activator of the acid or a dehydrating agent, for example, in the presence of isobutyl chloroformate, tetraethyl orthogonal acid, trimethyl orthoacetic acid, 2,2-dimethoxypropane, tetramethoxysilane, thionyl chloride, trichloroylvylphenylphosphate, , Ν, Ν'-dicyclohexylcarbodiimide,, Ν'-dicyclohexylcarbodiimide / H-hydroxysuccinimide, ^ n-dicyclohexylcarbodiimide / 1-hydroxybenzotriazo a, tetrafluoroborate 2- (1H-benzotriazol-1-yl) -1,1,3,3-tetramethyluronium, tetrafluoroborate 2- (1H-benzotriazol-1-yl) 1,1,3,3-tetramethyluronium / 1-hydroxybenzotriazole , Ν, Ν'-carbonyldiimidazole or triphenylphosphine / carbon tetrachloride, and optionally with a base such as pyridine, 4dimethylaminopyridine, дин-methylmorpholine or triethylamine, preferably at a temperature of from 0 to 150 ° C, preferably from 0 to 100 ° C. The reaction with an appropriate reactive compound can be carried out optionally in the presence of a tertiary organic base, such as triethylamine, α-ethyldiisopropylamine, α-methylmorpholine or pyridine, or with the use of anhydride in the presence of an appropriate acid at a temperature of from 0 to 150 ° C, preferably from 50 to 100 ° s

Subsequent esterification or subsequent amidation, it is advisable to carry out the interaction of the corresponding reactive carboxylic acid derivative with an appropriate alcohol or amine, as described above.

The subsequent oxidation of the sulfur atom is preferably carried out in a solvent or solvent mixture, for example in water, water / pyridine, acetone, methylene chloride, acetic acid, acetic acid / acetic anhydride, dilute sulfuric acid or trifluoroacetic acid, depending on the oxidant used, mainly on - 80 to 100 ° C.

To obtain the corresponding sulfinyl compound of general formula I, it is advisable to carry out the oxidation using one equivalent of the oxidizing agent used, for example using hydrogen peroxide in glacial acetic acid, trifluoroacetic acid or formic acid at a temperature of from 0 to 20 ° C or in acetone at a temperature of from 0 to 60 ° C, using a peracid, such as performic acid in glacial acetic acid or trifluoroacetic acid at a temperature of 0 to 50 ° C, or using m-chloroperbenzo hydrochloric acid in methylene chloride, chloroform or dioxane at a temperature of from -20 to 80 ° C, with sodium metaperiodate in

- 17 006080 aqueous methanol or ethanol at a temperature of from -15 to 25 ° C, using bromine in glacial acetic acid or aqueous acetic acid, optionally in the presence of a weak base, such as sodium acetate, using-bromosuccinimide in ethanol, using tert-butyl hypochlorite in methanol at a temperature of from -80 to -30 ° C, using iodobenzodichloride in aqueous pyridine at a temperature of from 0 to 50 ° C, using nitric acid in glacial acetic acid at a temperature of from 0 to 20 ° C, using chromic acid s in glacial acetic acid or in acetone at 0 to 20 ° C and with sulphuryl chloride in methylene chloride at -70 ° C, the complex obtained by this thioether-chloro expedient hydrolyzed with aqueous ethanol.

To obtain a sulfonyl compound of general formula I, the oxidation is carried out on the basis of the corresponding sulfinyl compound, preferably using one or more equivalents of the oxidizing agent used, or based on the corresponding mercapto compound, preferably using two or more equivalents of the used oxidizing agent, for example, using hydrogen peroxide in glacial acetic acid / acetic anhydride , trifluoroacetic acid or in formic acid at a temperature of from 20 to 100 ° C or acetone at a temperature of from 0 to 60 ° C, using a peracid, such as per-formic acid or m-chloroperbenzoic acid in glacial acetic acid, trifluoroacetic acid, methylene chloride or chloroform at a temperature of from 0 to 60 ° C, using nitric acid in glacial acetic acid acid at a temperature of 0 to 20 ° C, using chromic acid, sodium periodate or potassium permanganate in acetic acid, water / sulfuric acid or acetone at a temperature of 0 to 20 ° C.

Subsequent reduction of the nitro group is preferably carried out by hydrogenolysis, for example using hydrogen in the presence of a catalyst such as palladium on carbon or Raney nickel, in a solvent such as methanol, ethanol, ethyl acetate, dimethylformamide, dimethylformamide / acetone or glacial acetic acid, optionally with the addition of an acid, such as hydrochloric acid or glacial acetic acid, at a temperature of from 0 to 50 ° C, preferably, however, at room temperature, and at a hydrogen pressure of t 1 to 7 bar, preferably, however, from 3 to 5 bar.

The subsequent process for the preparation of the corresponding urea compound of the general formula I is expediently carried out using an inorganic cyanate or the corresponding isocyanate or carbamoyl chloride, preferably in a solvent such as dimethylformamide and optionally in the presence of a tertiary organic base such as triethylamine, at a temperature of from 0 to 50 ° C, preferably at room temperature.

The subsequent process for preparing the corresponding guanidino compound of general formula I is advantageously carried out by reacting with a transmitting amidino group such as amidine 3,5-dimethylpyrazole-1-carboxylic acid, preferably in a solvent such as dimethylformamide, optionally in the presence of a tertiary organic base such as triethylamine, with temperature from 0 to 50 ° C, preferably at room temperature.

When carrying out the reactions described above, reactive groups present under certain conditions, such as carboxy, hydroxy, amino, alkylamino, or imino groups, can be protected for the duration of the reaction with the usual protecting groups and again cleave these protective groups upon completion of the reaction.

As an example of a protecting group for a carboxy group, a trimethylsilyl, methyl, ethyl, tert-butyl, benzyl or tetrahydropyranyl group can be mentioned, an acetyl, trifluoroacetyl, benzoyl, ethoxycarbonyl, as an example of a protecting group for hydroxy, amino, alkylamino or imino, tert-butoxycarbonyl, benzyloxycarbonyl, benzyl, methoxybenzyl or 2,4-dimethoxybenzyl group, and for the amino group - additionally phthalyl group.

If necessary, the subsequent cleavage of the used protecting group can be carried out, for example, by hydrolyzing in an aqueous solvent, for example in water, isopropanol / water, tetrahydrofuran / water or dioxane / water, in the presence of an acid, such as trifluoroacetic acid, hydrochloric acid or sulfuric acid, or in the presence of an alkaline base, such as lithium hydroxide, sodium hydroxide or potassium hydroxide, at a temperature of from 0 to 100 ° C, preferably from 10 to 50 ° C.

However, cleavage of the benzyl, methoxybenzyl or benzyloxycarbonyl group is carried out, for example, by hydrogenolysis, in particular using hydrogen in the presence of a catalyst such as palladium on carbon, in a solvent such as methanol, ethanol, ethyl acetate, dimethylformamide, dimethylformamide / acetone or glacial acetic acid, optionally with the addition of an acid, such as hydrochloric acid or glacial acetic acid, at a temperature of from 0 to 50 ° C, but preferably at room temperature, and The pressure of hydrogen of from 1 to 7 bar, more preferably 3 to 5 bar.

- 18 006080

The methoxybenzyl group can also be cleaved in the presence of an oxidizing agent, such as cerium ammonium nitrate, in a solvent such as methylene chloride, acetonitrile or acetonitrile / water, at a temperature of from 0 to 50 ° C, more preferably at room temperature.

The 2,4-dimethoxybenzyl group is preferably, however, cleaved in trifluoroacetic acid in the presence of anisole.

The tert-butyl or tert-butyloxycarbonyl group is preferably cleaved by treatment with an acid, such as trifluoroacetic acid or hydrochloric acid, optionally with a solvent, such as methylene chloride, dioxane, ethyl acetate or ether.

The phthalyl group is preferably cleaved in the presence of hydrazine or a primary amine, such as methylamine, ethylamine or n-butylamine, in a solvent such as methanol, ethanol, isopropanol, toluene / water or dioxane, at a temperature of from 20 to 50 ° C.

In addition, the resulting chiral compounds of general formula I can be divided into their enantiomers and / or diastereomers.

Thus, for example, the compounds of general formula I, which are formed in the form of racemates, can be divided according to known methods (see LSFdeg Q. and EBE1 EH, Τορίοδ ίη §1Геёгёйеш 181гу, vol. 6, HUPeu! P1e5С1епсе. 1971) to their optical antipodes, and compounds of general formula I with at least 2 asymmetric carbon atoms can be divided on the basis of differences in their physicochemical properties by known methods, for example, chromatography and / or fractional crystallization, to their diastereomers, which, when formed, racemic form in n the following may be separated as described above, into the enantiomers.

The separation into enantiomers is preferably carried out by column separation on chiral phases or by recrystallization from an optically active solvent or by reacting with salt or derivatives, such as esters or amides, with an optically active substance, especially with acids and their activated derivatives or alcohols, which form the racemic compound. , and separation of the resulting mixture of diastereomeric salts or derivatives, for example, based on differences in their solubility, while of pure In these diastereomeric salts or derivatives, free antipodes can be released by exposure to an agent suitable for this purpose. As an example of the most commonly used optically active acids for the above purposes, one can mention Ό- and-forms of tartaric acid, dibenzoyl tartaric acid, di-tolyl tartric acid, malic acid, mandelic acid, camphorsulfonic acid, glutamic acid, acetylglutamic acid, aspartic acid , Α-acetyl asparaginic acid or quinic acid. An example of an optically active alcohol is (+) - or (-) - menthol, and as an example of an optically active acyl moiety in amides, you can call the (+) - or (-) - menthyloxycarbonyl moiety.

In addition, the compounds of the formula I obtained can be converted into their salts, primarily into their physiologically acceptable salts suitable for pharmaceutical use, with inorganic or organic acids. Examples of suitable acids include hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, fumaric acid, succinic acid, lactic acid, citric acid, tartaric acid, maleic acid or methanesulfonic acid.

In addition, the new compounds of the formula I obtained in this way, if they contain a carboxy group, can be converted, if necessary, into their salts with inorganic or organic bases, primarily their physiologically acceptable salts suitable for pharmaceutical use. Examples of suitable bases include sodium hydroxide, potassium hydroxide, cyclohexylamine, ethanolamine, diethanolamine and triethanolamine.

The compounds of the general formulas νΠ-ΧΠ used as starting materials are partly known from the literature, or they are obtained by methods known from the literature, or they can be obtained by the methods described above and in the following examples. For example, compounds of general formula IX are described in German application 19824922.5. In addition, compounds of general formula XI can be obtained from compounds of general formula I, in which K ₄ is a C _1-4 alkylphenyl substituted hydroxy group in the alkyl moiety, for example, by reaction with alkyl or arylsulfonyl chlorides.

As mentioned above, the new compounds of the general formula I, in which K ₁ is a hydrogen atom or a prodrug residue, have valuable pharmacological properties, primarily inhibiting effect on various kinases, mainly on receptor kinases, such as ΕΕΕΡΕΡΕΡ, ΡΌΟΕΚα, ΡΌΟΕΚβ, ECEC1 , ESEKZ, ESEK, NEK2, UE1K and NSEC, as well as for complexes of SOK (cyclin-dependent kinases (susnp bepebepktakek)), such as SEEK SEK2, SEKZ, SEK4, SEK5, SEEK6, SEK7, SEK8 and SEK9, such as their content and heart rate; (A, B1, B2, C, Ό1, 2, Ό3, E, E, C1, C2, H, I, and K) and in sup provided a clear cyclin, on the proliferation of cultivated human cells, particularly endothelial cells, such as angiogenesis, but also on the proliferation of other cells, particularly tumor cells.

The biological properties of the new compounds were investigated by the standard method as described below.

- 19 006080

Human endothelial cells of the human umbilical cord (ΗυνΕΤ) were cultured in ΓΜΌΜ medium (С1Ьсо ВК) supplemented with 10% fetal calf serum (FTS) (81dta company), 50 μM β mercaptoethanol (Iika company), standard antibiotics, 15 μg / ml growth factor endothelial cells (ECC8, SoyagonGeeFlTFs1Pgobisk) and 100 μg / ml of heparin (81gta), in gelatin-coated culture plates (0.2% gelatin, 8chm firm) at 37 ° C and 5% CO ₂ content in a water-saturated atmosphere.

For the study of the inhibitory activity of the compounds according to the invention, the cells were kept on a starvation diet for 16 hours, i.e. in culture medium without growth factors (ECC8 + heparin). Next, the cells were separated from the culture plates with trypsin / EDTA and washed once in serum-containing medium. After that, the cells were sown on the plates in the amount of 2.5x10 cells per well.

Cell proliferation was stimulated with 5 ng / ml νΕΟΕ165 (vascular endothelial growth factor (autobiotic), Η. \ Uek.11. SVR Hypertechnology) and 10 μg / ml heparin. 6 wells of each plate were used as a control, without stimulating the cells in them.

The compounds according to the invention were dissolved in 100% dimethyl sulfoxide and in various dilutions in triplicate were added to the cultures, the maximum concentration of dimethyl sulfoxide was 0.3%.

Cells were incubated for 76 hours at 37 ° C, after which ³ H-thymidine (0.1 μCi / well, Laytayat) was added over the next 16 hours. Then the radioactively labeled cells were immobilized on filter canvases and the bound (built-in) radioactivity was determined using a β-radiation counter. To determine the inhibitory activity of the compounds according to the invention, the average value obtained for unstimulated cells was subtracted from the average value obtained for factor-stimulated cells (in the presence or absence of the compounds according to the invention).

The relative cell proliferation was calculated as a percentage of the control (ΗυVΕС-cells without inhibitor) and the concentration of the active substance was determined, at which 50% inhibition of the proliferation of DS cells is achieved ").

In the experiments described above, for example, the following compounds (a) - (y) of general formula I were investigated, the inhibitory activity indices of which are given below.

(a) 3-Ζ- [1- (4- (piperidin-1 -ylmethyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (b) 3 ^ - [(1- (4- ( piperidin-1-methyl) anilino) -1-phenylmethylene] -6-carbamoyl-2-indolinone, (c) 3-Ζ- [1 - (4- (piperidin-1-methylmethyl) anilino) -1-phenylmethylene] - 6-methoxycarbonyl-2-indolinone, (g) 3 ^ - [1- (4- (dimethylaminomethyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (e) 3-Ζ- [1 - ( 4 - ((2,6-dimethylpiperidin-1-yl) methyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2indolinone, (e) 3 -Ζ- [1 - (4- (no. (2-dimethylaminoethyl) -Noacetylamino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (g) 3 -Ζ- [1 - (4- (Ν- (3-dimethylamine propyl) -Noacetylamino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (h) 3 ^ - [1- (4- (No. (2-dimethylaminoethyl) -Nmethylsulfonylamino) anilino) -1- phenylmethylene] -6 ethoxycarbonyl-2-indolinone, (and) 3 ^ - [1- (4- (dimethylaminomethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone, (k) 3 -Ζ- [1 - (4- (no. Acetyl-dimethylaminocarbonylmethylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone, (l) 3-Ζ- [1 - (4-ethylaminomethylanilino) -1-phenylmethylene] -6-methoxycarbonyl -2-Indolinone, (m) 3 -Ζ- [1 - (4- (1-methylimidazol-2-yl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone, (n) 3 -Ζ- [1- (4- (No. dimethylaminomethylcarbonyl-No.methylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone, (o) 3 -Ζ- [1 - (4- (No. (2-dimethylaminoethyl) -№methylsulfonylamino) anilino) - 1-phenylmethylene] -6methoxycarbonyl-2-indolinone, (p) 3 -Ζ- [1- (4- (Ν- (3-dimethylaminopropyl) -Nomethylsulfonylamino) anilino) -1-phenylmethylene] -6methoxycarbonyl-2-indolinone, (p) 3 -Ζ- [1 - (4- (No. dimethylaminocarbonylmethyl-No. methylsulfonylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone, (c) 3 -Ζ- [1 - (4- ( No. ((2-dimethylaminoethyl) carbonyl) -Nomethylamino) anilino) -1-phenylmethylene] -6methoxycarbonyl-2-indolinone, (t ) 3 -Ζ- [1 - (4- (No. (2-dimethylaminoethyl) -Noacetylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone and (y) 3-Ζ- [1- (4 -methylaminomethylanilino) -1 -phenylmethylene] -6-methoxycarbonyl-2-indolinone.

The following table presents the results obtained in the experiments.

- 20 006080

The compounds of general formula I, due to their inhibitory effect on cell proliferation, primarily endothelial and tumor cells, are suitable for the treatment of diseases in which the proliferation of cells, especially endothelial cells, plays a certain role.

Thus, for example, the proliferation of endothelial cells and the associated formation of new vessels are decisive factors in the progression of tumors (Tölktap T et al., No. 11gs 339, 58-61 (1989); Napayap. And Tölltak 1., Ce1186, 353 -365 (1996)). In addition, the proliferation of endothelial cells is of particular importance in hemangiomas, in metastasis, in rheumatoid arthritis, in psoriasis, and in the formation of new eye vessels (To1ktap 1., No. 1 and Meb. 1, 27-31 (1995)). The therapeutic efficacy of inhibitors of the proliferation of endothelial cells was confirmed in animal models, for example, Okay et al., As well as Ragapf et al. (O.Keschu M.8. Et al., Ce11 88, 277285 (1997); Ragapd 8 and others, Proc. No. 11. Assab. 8c1. I8A 93, 2002-2007 (1996)).

Accordingly, the compounds of general formula I, their tautomers, their stereoisomers or their physiologically acceptable salts are suitable, for example, for the treatment of tumors (in particular squamous cell carcinoma, astrocytomas, Kaposi's sarcoma, glioblastoma, lung cancer, bladder cancer, cervical and cervical cancer areas, melanoma, ovarian cancer, prostate cancer, breast cancer, small cell lung cancer, glioma, colon cancer, urogenital cancer and gastrointestinal cancer, as well as cancer of the blood, such as multiple myeloma), psoriasis, arthritis (for example, rheumatoid arthritis), hemangiomas, opaquefiroma, eye diseases (for example, diabetic retinopathy), neovascular glaucoma, kidney disease (for example, glomerulonephritis), diabetic nephropathy, malignant nephrosclerosclerosis, for example kidney disease (for example, glomerulonephritis), diabetic nephropathy, malignant nephrosclerosclerosis, for example and glomerulopathy, fibrotic diseases (for example, cirrhosis of the liver), caused by proliferation of mesangial cell diseases, arteriosclerosis, lesions of the nervous tissue, and for suppressing Re-occlusion of blood vessels after treatment with a balloon catheter, with vessel prosthetics or after application, respectively, the introduction of mechanical devices to maintain the patency of the vessels (eg, stents) or other diseases in which cell proliferation or angiogenesis play a certain role.

Due to their biological properties, the compounds according to the invention can be used individually or in combination with other pharmacologically active compounds, for example, for the therapeutic treatment of tumors with monotherapy or in combination with other anti-tumor therapeutic agents, for example in combination with topoisomerase inhibitors (for example, etoposide), with antimitotic agents (for example, vinblastine, taxol), with compounds interacting with nucleic acids (for example, cis-platin, cycle ofosfamide, adriamycin), with hormone antagonists (for example, tamoxifen), with inhibitors of metabolic processes (for example, 5-RI, etc.), with cytokines (for example, interferons), with inhibitors of kinases, with antibodies or in combination with radiation therapy, etc. In such combinations, the active ingredients can be administered either simultaneously or sequentially, respectively, using the active ingredients in combination with non-pharmacological types of therapy simultaneously or sequentially.

For pharmaceutical use, the compounds according to the invention are administered, as a rule, to warm-blooded vertebrates, especially to humans, in doses of from 0.01 to 100 mg / kg body weight, preferably from 0.1 to 20 mg / kg. For the preparation of drugs, such compounds are processed together with one or more conventional inert carriers and / or diluents, for example, corn starch, lactose, cane sugar, microcrystalline cello, magnesium sterate, polyvinylpyrrolidone, citric acid, tartaric acid, water, water / ethanol, water / glycerin, water / sorbitol, water / polyethylene glycol, propylene glycol, stearyl alcohol, carboxymethylcellulose, or fat-containing substances, such as rzhdenny fat or suitable mixtures thereof to produce conventional galenic forms, such as tablets, dragees, capsules, powders, injectable solutions, ampoules, suspensions, solutions, sprays or suppositories.

Below the invention is illustrated by examples.

The following examples use the following abbreviations:

EMOC - 9-fluorenylmethoxycarbonyl,

HOBT - 1-hydroxy-1H-benzotriazole,

TBTU - O-benzotriazol-1-yl tetrafluoroborate - ^^ №, №-tetramethyluronium,

DBU is 1,8-diazabicyclo [5.4.0] undec-7-en.

Getting the original connections

Example I to obtain a solid phase.

2.0 g of Rinka resin (MBHA-resin, firm Noc ^ substitute) is placed for swelling in 30 ml of dimethylformamide. Next, add 40 ml of 30% piperidine in dimethylformamide and shake for 7 minutes to remove the protective EMOS group. Then the resin is washed several times with dimethylformamide. Next, add 0.4 g of 2-indolinone-6-carboxylic acid (obtained by analogy with the method described in Bapdepsk et al., ΙιΐδΙιΐδ ЬеЬщ5 Αηη. Sket. 499, 201-208 (1932)), 297 mg HOBT, 706 mg TBTU and 0.9 ml of α-ethyldiisopropylamine in 30 ml of dimethylformamide and shake for 1 hour. After that, the solution is suction filtered and the resin is washed five times with 30 ml of dimethylformamide and three times with 30 ml of methylene chloride. For drying, the resin is flushed with nitrogen.

Yield: 1.9 g of saturated resin.

Example II to obtain a solid phase.

1.9 g of the resin obtained according to Example I was stirred for 3 hours at 110 ° C together with 6 ml of acetic anhydride and 6 ml of orthobenzoic acid triethyl ester. After that, the mixture is allowed to cool and the resin is washed with dimethylformamide, and then with methylene chloride.

Yield: 1.9 g wet resin.

Analogously to example II, the following saturated resins are obtained:

(1) containing 3-2- (1-ethoxymethylene) -6-carbamoyl-2-indolinone resin: said resin is obtained by reacting the resin obtained according to example I with trimethyl ortoformate;

(2) containing 3-2- (1-methoxy-1-methylmethylene) -6-carbamoyl-2-indolinone resin: this resin is obtained by reacting the resin obtained in Example I with trimethyl orthoacetic acid;

(3) containing 3-2- (1-methoxy-1-ethylmethylene) -6-carbamoyl-2-indolinone resin: this resin is obtained by reacting the resin obtained in Example I with orthopropionic acid trimethyl ester;

(4) containing 3-2- (1-methoxy-1-propylmethylene) -6-carbamoyl-2-indolinone resin: this resin is obtained by reacting the product of Example I with orthobutyric acid trimethyl ester.

Example III No. (4-Nitrophenyl) - # Methyl methanesulfonamide.

3.0 g of methyl №-4-nitroaniline is dissolved in 20 ml of pyridine and then 2.4 g of methanesulfonic acid chloride are added dropwise at room temperature. The mixture is stirred for 12 hours at room temperature. After that, the mixture is poured into water, the precipitated precipitate is filtered off and dried at 50 ° C in vacuum.

Output: 4.0 g (87% of theory),

K-value: 0.5 (silica gel, ethyl acetate / toluene in a ratio of 7: 3),

1 _PL : 107-108 ° C.

Example IV No. (2-Dimethylaminoethyl) -Mnomethylsulfonyl-4-nitroaniline.

38.9 g of methyl sulfonyl-4-nitroaniline are dissolved in 2.0 l of acetone, 51.9 g of 1-chloro-2 dimethylaminoethane, 77.4 g of potassium carbonate and 5.0 g of sodium iodide are added and the mixture is stirred for a total of 4 days at 50 ° C, while 12 hours after the start of stirring, 25.9 g of 1-chloro-2-dimethylaminoethane, 49.8 g of potassium carbonate and 5.0 g of sodium iodide in 500 ml of acetone are added, and after 36 hours 26.0 g of 1-chloro-2-dimethylaminoethane, 50.0 g of potassium carbonate and 5.0 g of sodium iodide in 100 ml of acetone are added. After that, the mixture is filtered and the filtrate is concentrated. The residue is stirred in ether, suction filtered and dried at 40 ° C.

Yield: 25.3 g (49% of theory),

K-value: 0.5 (silica gel, methylene chloride / methanol / ammonia in a ratio of 9: 1: 0.1),

C _p H ₁₇ SCHO ₄ 8, mass spectrum (E 8C t / ζ = 288 [M + H ⁺ ].

Analogously to example IV, the following compounds are obtained:

- 22 006080 (1) 4- [No. (3-dimethylaminopropyl) -Nomethylsulphonylamino] nitrobenzene, (2) No. of carboxymethyl-No.methylsulfonyl-4-nitroaniline, (3) No. of cyanomethyl-No.methylsulfonyl-phenylenediamine, (4) 4- [No. (2- (No.benzyl-No.methylamino) ethyl) -Mnomethylsulfonylamino] nitrobenzene, (5) 4- [No. (3-phthalimido-2-ylpropyl) -№methylsulfonylamino] nitrobenzene, (6) 4- [No. ( 3- (No.benzyl-No.methylamino) propyl) -№methylsulfonylamino] nitrobenzene.

Example V. No. (Dimethylaminocarbonylmethyl) -Nomethylsulfonyl-4-nitroaniline.

7.0 g of the No. of carboxymethyl No. of methylsulfonyl-4-nitroaniline, 2.5 g of dimethylamine hydrochloride, 8.1 g of TBTU and 3.9 g of HOBT are dissolved in 125 ml of dimethylformamide and 17.6 ml of ethyl diisopropylamine are added at 0 ° C. The mixture is stirred for 4 hours at room temperature, diluted with 1 l of water and the precipitate formed is suction filtered. After washing with water, ethanol and ether, the residue is dried at 70 ° C in vacuo.

Yield: 5.3 g (69% of theory),

K-value: 0.40 (silica gel, methylene chloride / methanol in the ratio 9: 1), mass spectrum (ECC t / ζ = 300 [M-H ^- ].

Analogously to example V, the following compounds are obtained:

(1) 4 - [(dimethylaminocarbonylmethyl) amino] nitrobenzene: this compound is obtained from 4 (carboxymethylamino) nitrobenzene and dimethylamine hydrochloride;

(2) 4- (No. methylaminocarbonylmethyl-No. methylsulfonylamino) nitrobenzene: the title compound is obtained from No. of carboxymethyl-No. methylsulfonyl-4-nitroaniline and methylamine hydrochloride;

(3) 4 - [(no. (Methylcarbamoylmethyl) -Nomethylamino) methyl] nitrobenzene: the title compound is obtained from 4 - [(carboxymethyl-nomethylamino) methyl] nitrobenzene and methylamine hydrochloride;

(4) 4 - [(no. (Dimethylcarbamoylmethyl) -Nomethylamino) methyl] nitrobenzene: the indicated compound is obtained from 4 - [(carboxymethyl-nomethylamino) methyl] nitrobenzene and dimethylamine hydrochloride.

Example VI 4- [No. (2-Dimethylaminoethyl) -N. acetylamino] nitrobenzene.

3.6 g of 4- (2-dimethylaminoethylamino) nitrobenzene (prepared according to the method described in Saul et al., 1. At. C. et. 8oc. 91, 5136 (1969)) is dissolved in 50 ml of methylene chloride and 5.0 ml are added triethylamine. 1.3 ml of acetyl chloride is slowly added dropwise to this mixture at room temperature and the mixture is stirred for 2 hours at room temperature. After that, additional 5.0 ml of triethylamine and 1.3 ml of acetyl chloride are added and refluxed for a further 2 hours. The solvent is distilled off, the residue is dissolved in ethyl acetate and the organic phase is extracted twice by shaking with water. After drying over MgO _{4, the} solvent is distilled off and the residue is dried in vacuo.

Yield: 2.0 g (45% of theory),

K-value: 0.55 (silica gel, methylene chloride / methanol / ammonia in the ratio 9: 1: 0.1), ^C 12Η17 ^N 3 ^O 3 ^, mass spectrum (EM): t / ζ = 252 [M + H ⁺ ].

Analogously to example VI, the following compounds are obtained:

(1) 4- [No. (3-dimethylaminopropyl) -Noacetylamino] nitrobenzene: the indicated compound is obtained from 4- (3-dimethylaminopropylamino) nitrobenzene, prepared according to the method described in SaBau et al., 1. At. Syt 8os 91, 5136 (1969) and acetyl chloride;

(2) 4- [No. (2-dimethylaminoethyl) -No-propionylamino] nitrobenzene: the title compound is obtained from 4- (2-dimethylamino-ethylamino) nitrobenzene and propionyl chloride;

(3) 4- [No. acetyl-No (dimethylaminocarbonylmethyl) amino] nitrobenzene: the title compound is obtained from 4- [No. (dimethylaminocarbonylmethyl) amino] nitrobenzene and acetyl chloride;

(4) 4- [No. (2-dimethylaminoethyl) -N.butyrylamino] nitrobenzene: the title compound is obtained from 4- (2-dimethylaminoethylamino) nitrobenzene and butyryl chloride;

(5) 4- [No. (2-dimethylaminoethyl) -№ isobutyrylamino] nitrobenzene: the title compound is obtained from 4- (2-dimethylaminoethylamino) nitrobenzene and isobutyryl chloride;

(6) 4- [No. (2-dimethylaminoethyl) -Nobenoylamino] nitrobenzene: the title compound is obtained from 4- (2-dimethylaminoethylamino) nitrobenzene and benzoyl chloride;

(7) 4- [no. (2-dimethylaminoethyl) -Noacetylamino] -1,3-dinitrobenzene: the title compound is obtained from 4- (2-dimethylaminoethylamino) -1,3-dinitrobenzene and acetyl chloride;

(8) 4- [No. (2-dimethylaminoethyl) -No (furan-2-carbonyl) amino] nitrobenzene: the said compound is obtained from 4- (2-dimethylaminoethylamino) nitrobenzene and furan-2-carbonyl chloride;

(9) 4- [No. (2-dimethylaminoethyl) -No (2-methoxybenzoyl) amino] nitrobenzene: the compound is obtained from 4- (2-dimethylaminoethylamino) nitrobenzene and 2-methoxybenzoyl chloride;

(10) 4- [No. (2-dimethylaminoethyl) -No (pyridine-3-carbonyl) amino] nitrobenzene: the compound is obtained from 4- (2-dimethylaminoethylamino) nitrobenzene and nicotinic acid chloride;

(11) 4- [No. (2-dimethylaminoethyl) -No (phenylacetyl) amino] nitrobenzene: the compound is obtained from 4- (2-dimethylaminoethylamino) nitrobenzene and phenylacetyl chloride;

- 23 006080 (12) 4- [№ (2-dimethylaminoethyl) -Noacetylamino] -3-bromonitrobenzene: the above compound is obtained from 4- [No. (2-dimethylaminoethyl) amino] -3-bromo-nitrobenzene and acetyl chloride;

(13) Acryloyl-Methyl-4-nitroaniline: this compound is obtained from 4-methylaminonitrobenzene and acrylic acid chloride;

(14) Acryloyl-n-isopropyl-4-nitroaniline: this compound is obtained from 4-isopropylaminonitrobenzene and acrylic acid chloride;

(15) No. Acryloyl-No.benzyl-4-nitroaniline: the title compound is obtained from 4-benzylaminonitrobenzene and acrylic acid chloride;

(16) No. of bromoacetyl-#methyl-4-nitroaniline: the compound is obtained from 4-methylaminonitrobenzene and bromoacetyl chloride;

(17) Bromoacetyl-No. Isopropyl-4-nitroaniline: the title compound is obtained from 4-isopropylaminonitrobenzene and bromoacetyl chloride;

(18) No. of bromoacetyl-No.Benzyl-4-nitroaniline: the compound is obtained from 4-benzylaminonitrobenzene and bromoacetyl chloride.

Example VII No. (Dimethylaminomethylcarbonyl) -methyl-4-nitroaniline.

1.8 g of dimethylamine hydrochloride and 5.5 g of potassium carbonate are placed in 80 ml of acetone and 4.2 g of bromoacetyl-methyl-4-nitroaniline are added at room temperature in three portions. The mixture is stirred for 12 hours at room temperature. After that, the mixture is filtered and the filtrate is concentrated. The residue is dissolved in ethyl acetate, washed twice with water, dried over sodium sulfate and finally evaporated on a rotary evaporator.

Yield: 2.8 g (79% of theory),

K-value: 0.5 (silica gel, ethyl acetate / methanol in the ratio 7: 3), ν 121-122 ° С.

Analogously to example VII receive the following compounds:

(1) No. (piperidin-1-methylmethylcarbonyl) -Nomethyl-4-nitroaniline, (2) No. (morpholin-4-ylmethylcarbonyl) -Nomethyl-4-nitroaniline, (3) No. [(4-benzylpiperazin-1- or methylcarbonyl] -№methyl-4-nitroaniline, (4) no. (pyrrolidin-1-methylmethylcarbonyl) -№methyl-4-nitroaniline, (5) no. [(α-aminocarbonylmethyl-NO. methylamino) methylcarbonyl] -methyl-4 -nitroaniline, (6) No. [(No.Benzyl-No.methylamino) methylcarbonyl] -Nomethyl-4-nitroaniline, (7) No. [di (2-methoxyethyl) aminomethylcarbonyl] -№methyl-4-nitroaniline, (8) No. (dimethylaminomethylcarbonyl) -Noisopropyl-4-nitroaniline, (9) No. (piperidine-1 -methylcarbonyl) -Noisopropyl-4-nitro aniline, (10) No. [(4-tert-butoxycarbonylpiperazin-1-yl) methylcarbonyl] ^ - isopropyl-4-nitroaniline, (11) No. [(No.Benzyl ^ -methylamino) methylcarbonyl] -№benzyl-4-nitroaniline, (12) No. (dimethylaminomethylcarbonyl) -Nbenzyl-4-nitroaniline, (13) No. (piperidine-1 -methylcarbonyl) -N.benzyl-4-nitroaniline, (14) No. [di (2-hydroxyethyl) aminomethylcarbonyl] -Nomethyl -4-nitroaniline, (15) No. [(No. (2-methoxyethyl) -Nomethylamino) methylcarbonyl] -Nomethyl-4-nitroaniline, (16) No. [(No. (2-dimethylaminoethyl) -Nmethylamino) methylcarbonyl] - Methyl-4-nitroaniline, (17) No. [(4-methylpiperazin-1-yl) methylcarbonyl] -Nomethyl-4-nitroaniline, (18) No. [(imidazol-1-yl) methylcarbonyl] -Nomethyl-4-nitroaniline, (19) No. [(phthalimido-2-yl) methylcarbonyl] -№methyl-4-nitroaniline.

Example VIII. No. [(2-Dimethylaminoethyl) carbonyl] -Nobenzyl-4-nitroaniline.

0.5 g of dimethylamine hydrochloride, 1.1 ml of triethylamine and 1.2 g of Acryloyl-No. Benzyl-4 nitroaniline are dissolved in 50 ml of methanol and stirred for 24 hours at room temperature. After that, the mixture is concentrated. The residue is purified on a column of alumina (activity 2-3) using methylene chloride / ethanol in a ratio of 50: 1 as a solvent.

Output: 1.4 g (98% of theory),

K-value: 0.8 (aluminum oxide, methylene chloride / ethanol in a ratio of 20: 1),

V 73 ° C.

Analogously to example VIII receive the following compounds:

(1) No. [(2-Dimethylaminoethyl) carbonyl] -Noisopropyl-4-nitroaniline: the title compound is obtained from acacryloyl-isopropyl-4-nitroaniline and dimethylamine hydrochloride;

(2) No. [(2-dimethylaminoethyl) carbonyl] -Nomethyl-4-nitroaniline: the title compound is obtained from acacryloyl-methyl4-nitroaniline and dimethylamine hydrochloride;

(3) No. [(2- (4-tert-butoxycarbonylpiperazin-1-yl) ethyl) carbonyl] -Nomethyl-4-nitroaniline: the compound was obtained from Acryloyl-Nmethyl-4-nitroaniline and Ν-tert-butoxycarbonylpiperazine ;

(4) No. [(2- (piperidin-1-yl) ethyl) carbonyl] -Nomethyl-4-nitroaniline: the compound is obtained from Acryloyl-Nomethyl-4-nitroaniline and piperidine;

- 24 006080 (5) No. [(2-Sch-benzyl-No. methylamino) ethyl) carbonyl] -Mnomethyl-4-nitroaniline: the specified compound is obtained from No. acryloyl-No.methyl-4-nitroaniline and M-benzyl-L- methyl amine.

Example IX 4- (4-Methylpiperazin-1-yl) nitrobenzene.

31.5 g of 4-chloro-1-nitrobenzene are combined with 44.4 ml of 1-methylpiperazine and stirred for 18 hours at 90 ° C. After that, the solution is poured into a mixture of ice water and the precipitated precipitate is separated by vacuum filtration, washed with water and recrystallized from ethanol / water (1: 1). The residue is dried in vacuum at 75 ° C.

Output: 44.0 g (99% of theory),

I ^ -value: 0.5 (silica gel, methylene chloride / methanol 10: 1),

1 pl: 108-112 ° C.

Analogously to example IX receive the following compounds:

(1) No. (2-dimethylaminoethyl) -Nomethyl-4-nitroaniline: the title compound is obtained from 1-fluoro-4-nitrobenzene and 1-dimethylamino-2-methylamino-ethane;

(2) No. (3-dimethylaminopropyl) -Nomethyl-4-nitroaniline: the compound is obtained from 1-fluoro-4-nitrobenzene and 1-dimethylamino-3-methylaminopropane;

(3) 4- (N-carboxymethylamino) nitrobenzene: the title compound is prepared from 1-fluoro-4-nitrobenzene and glycine;

(4)-cyclohexyl-p-phenylenediamine: the compound is obtained from 1-fluoro-4-nitrobenzene and cyclohexylamine;

(5) 6-Sch- (2-dimethylaminoethyl) -Mnomethylsulfonylamino] -3-phthalimido-2-ylnitrobenzene: the above compound is obtained from 2-nitro-4-phthalimido-2-ylfluorobenzene, N- (2-dimethylaminoethyl) methanesulfonamide and sodium hydride as base;

(6) 6-Shch- (2-dimethylaminoethyl) -Mnomethylsulfonylamino] -1,3-dinitrobenzene: the compound is obtained from 2,4-dinitrochlorobenzene, No. (2-dimethylaminoethyl) methanesulfonamide and sodium hydride as the base;

(7) 4-Shch- (2-dimethylaminoethyl) -Mnomethylsulfonylamino] -3-chloronitrobenzene: the compound is obtained from 2-fluoro-5-nitrochlorobenzene, Y- (2-dimethylaminoethyl) methanesulfonamide and sodium hydride as the base;

(8) 4- (2-dimethylaminoethylamino) -1,3-dinitrobenzene: the title compound is prepared from 1-chloro-2,4-dinitrobenzene and Ν,-dimethylethylenediamine;

(9) 4-Shch- (2-dimethylaminoethyl) -No (ethylsulfonyl) amino] nitrobenzene: the specified compound is obtained from 1-fluoro-4-nitrobenzene, no. (2-dimethylaminoethyl) ethanesulfonamide and sodium hydride as the base;

(10) 4-Shch- (2-dimethylaminoethyl) -No (propylsulfonyl) amino] nitrobenzene: the compound is obtained from 1-fluoro-4-nitrobenzene, No (2-dimethylaminoethyl) propanesulfonamide and sodium hydride as the base;

(11) 4- | L- (2-dimethylaminoethyl) -N (butylsulfonyl) amino] nitrobenzene: the compound is obtained from 1-fluoro-4-nitrobenzene, Y- (2-dimethylaminoethyl) butanesulfonamide and sodium hydride as the base;

(12) 4- | L- (2-dimethylaminoethyl) -N (benzylsulfonyl) amino] nitrobenzene: the compound is obtained from 1-fluoro-4-nitrobenzene, N- (2-dimethylaminoethyl) -C-phenylmethanesulfonamide and sodium hydride as grounds;

(13) 4-Shch- (2-dimethylaminoethyl) -No (phenylsulfonyl) amino] nitrobenzene: the compound is obtained from 1-fluoro-4-nitrobenzene, N- (2-dimethylaminoethyl) benzenesulfonamide and sodium hydride as the base;

(14) 4- | L- (2-dimethylaminoethyl) -N (isopropylsulfonyl) amino] nitrobenzene: the compound is obtained from 1-fluoro-4-nitrobenzene, Y- (2-dimethylaminoethyl) isopropylsulfonamide and sodium hydride as the base;

(15) 4- [Y- (2-dimethylaminoethyl) amino] -3-bromonitrobenzene: the title compound is obtained from 2-bromo-1-fluoro-4-nitrobenzene and Ν,-dimethylethylenediamine;

(16) 4-isopropylaminonitrobenzene: the compound is obtained from 1-fluoro-4-nitrobenzene and isopropylamine;

(17) 4-benzylaminonitrobenzene: the said compound is obtained from 1-fluoro-4-nitrobenzene and benzylamine.

Example X. 4- (Imidazol-4-yl) nitrobenzene.

9.5 g of 2-phenylimidazole is carefully dissolved in 50 ml of concentrated sulfuric acid and 5.8 g of ammonium nitrate is added to this solution at 0 ° C. After stirring for another 60 minutes at 0 ° C, the mixture is poured into ice-water, basified with ammonia water and the precipitated precipitate is suction filtered and recrystallized from ethanol.

Output: 8.0 g (64% of theory),

I _g value: 0.6 (silica gel, ethyl acetate / ethanol 10: 1),

OD ^,

- 25 006080 mass spectrum: t / = 189 [M ^- ].

Analogously to example X, the following compounds are obtained:

(1) 4- (imidazol-2-yl) nitrobenzene: said compound is obtained from 4- (imidazol-2-yl) benzene;

(2) 4- (5-methylimidazol-4-yl) nitrobenzene: the indicated compound is obtained from 4-methyl-5phenylimidazole (1. Heterogus1. Sbet. 20: 1277-1281 (1983)).

Example XI. 4- (2- (Imidazol-4-yl) ethylene) nitrobenzene.

1.5 g of 4-nitrobenzaldehyde and 7.45 g of chloride (L-tritylimidazol-4-ylmethyl) triphenylphosphonium are dissolved in 75 ml of tetrahydrofuran, and 3.0 ml of DBU is added dropwise to this solution at room temperature. After stirring for the next 120 minutes at room temperature, the mixture is poured into water and the precipitate formed is suction filtered. The product is dissolved in 25 ml of 1N. hydrochloric acid and refluxed for 4 hours. After that, it is neutralized with ammonia water, extracted with ethyl acetate and the organic phase is washed with water, dried over sodium sulfate and evaporated. The residue is purified on a silica gel column using methylene chloride / methanol (10: 1) as a solvent.

Output: 1.0 g (47% of theory), ^ (- value: 0.6 (silica gel, ethyl acetate / ethanol in a ratio of 10: 1),

1 _PL : 185-188 ° C.

Example XII. 4- (Piperidin-1-methylmethyl) nitrobenzene.

40.0 g of 4-nitrobenzyl bromide is dissolved in 500 ml of methylene chloride, 51.5 ml of triethylamine are added and 18.3 ml of piperidine is carefully added dropwise. At the end of the exothermic reaction, the mixture is heated under reflux for a further 30 minutes. After cooling, it is washed with water and the organic phase is dried over sodium sulphate. Finally, the organic phase is concentrated.

Yield: 36.3 g (89% of theory) ^ {- value: 0.6 (silica gel, methylene chloride / methanol 9: 1), 12 ^C ^Η 16 ^N 2 ^O ^2, MS: m / ζ = 221 [M ⁺ ].

Analogously to example XII receive the following compounds:

(1) 4 - [(2,6-dimethylpiperidin-1-yl) methyl] nitrobenzene, (2) 3 - (^ dimethylaminomethyl) nitrobenzene, (3) 4 - (dimetylaminomethyl) nitrobenzene, (4) 4- (2-dimethylaminoethyl) nitrobenzene, (5) 4- (2-diethylaminoethyl) nitrobenzene, (6) 4- (diethylaminomethyl) nitrobenzene, (7) 4- (No. benzyl-I-methylaminomethyl) nitrobenzene, (8) 4- ( No. Ethyl-I-methylaminomethyl) nitrobenzene, (9) 4- [No. (n-hexyl) -I-methylaminomethyl] nitrobenzene, (10) 4- (thiomorpholin-4-ylmethyl) nitrobenzene, (11) 4 - [(4 -methylpiperazin-1-yl) methyl] nitrobenzene, (12) 4- (imidazol-1-ylmethyl) nitrobenzene, (13) 4- [2- (4-hydroxypiperidin-1-yl) ethylamino] nitrobenzene, (14) 4 - [(3 Droxypyrrolidin-1-yl) methyl] nitrobenzene, (15) 4- (1,2,4-triazol-1-ylmethyl) nitrobenzene, (16) 4- (1,2,3-triazol-2-ylmethyl) nitrobenzene, (17) 4- (1,2,3-triazol-1-ylmethyl) nitrobenzene, (18) 4 - [(No. of ethoxycarbonylmethyl-I-methylamino) methyl] nitrobenzene, (19) 4- [(No. of aminocarbonylmethyl-I- methylamino) methyl] nitrobenzene, (20) 4- (azetidin-1-ylmethyl) nitrobenzene, (21) 4 - [(di (2-methoxyethyl) amino) methyl] nitrobenzene, (22) 4- [Y- (No.t -butoxycarbonyl-3-aminopropyl) -N-methylaminomethyl] nitrobenzene, (23) 4 - [(No.propyl-I-methylamino) methyl] nitrobenzene, (24) 4 - [(No. (2-dimethylaminoethyl) -Y-methylamino) methyl] nitrobenzene, (25) 4 - [(№ (3 -dimethylaminopropyl) -Y-methylamino) methyl] nitrobenzene, (26) 4 - [(no. (2-methoxyethyl) -I-methylamino) methyl] nitrobenzene, (27) 4 - [(no. (2-hydroxyethyl) -I- methylamino) methyl] nitrobenzene, (28) 4 - [(no. (dioxolan-2-ylmethyl) -H-methylamino) methyl] nitrobenzene, (29) 4- (3-oxopiperazin-1 -ylmethyl) nitrobenzene.

Example XIII 4 - [(No.Carboxymethyl-I-methylamino) methyl] nitrobenzene.

7.33 g of 4 - [(Ethoxycarbonylmethyl-I-methylamino) methyl] nitrobenzene is dissolved in 140 ml of ethanol, 34.0 ml of 1N is added. caustic soda and the mixture is stirred for half an hour at room temperature. After that, neutralize 34 ml of 1N. hydrochloric acid, the solvent is distilled off, the residue is dissolved

- 26 006080 in methylene chloride and extracted with water. The aqueous phase is concentrated and the residue is recrystallized from methylene chloride.

Yield: 5.43 g (84% of theory),

K _g value: 0.4 (silica gel, methylene chloride / methanol in the ratio 2: 1), ^C 10 ^Η 12 ^N 2 ^O 4 ^, mass spectrum: t / = 223 | Ν '|.

Example XIV. 4- (No. Ethylaminomethyl) nitrobenzene.

6.0 g of 4-nitrobenzyl bromide is dissolved in 25 ml of ethanol, mixed with 25 ml of a 10% ethanolic ethylamine solution and refluxed for 2 hours. After that, the solution is evaporated on a rotary evaporator, the residue is dissolved in methylene chloride and washed with dilute sodium hydroxide solution. Finally, the organic phase is concentrated.

Output: 2.3 g (46% of theory),

To _g value: 0.2 (silica gel, methylene chloride / methanol in a ratio of 9: 1),

C9H12 ^ O2, mass spectrum (E8C: t / ζ = 179 [M – H ^- ].

Analogously to example XIV receive the following compounds:

(1) 4- [No. (4-chlorobenzyl) aminomethyl] nitrobenzene, (2) 4- (No. Cyclohexylaminomethyl) nitrobenzene, (3) 4- (No. Isopropylaminomethyl) nitrobenzene, (4) 4- (No. Propylaminomethyl) nitrobenzene, ( 5) 4- (No.methylaminomethyl) nitrobenzene, (6) 4- (No. butylaminomethyl) nitrobenzene, (7) 4- (No. methoxycarbonylmethylaminomethyl) nitrobenzene, (8) 4- (No.benzylaminomethyl) nitrobenzene, (9) 4- (aminomethyl) ) nitrobenzene, (10) 4- (pyrrolidin-1-ylmethyl) nitrobenzene, (11) 4- (morpholin-4-ylmethyl) nitrobenzene, (12) 4- (hexamethyleneiminomethyl) nitrobenzene, (13) 4- (4-hydroxypiperidine -1-ylmethyl) nitrobenzene, (14) 4- (4-methoxypiperidin-1-ylmethyl) itrobenzene, (15) 4- (4-methylpiperidin-1-ylmethyl) nitrobenzene, (16) 4- (4-ethylpiperidin-1-ylmethyl) nitrobenzene, (17) 4- (4-isopropylpiperidin-1-ylmethyl) nitrobenzene, (18) 4- (4-phenylpiperidin-1-ylmethyl) nitrobenzene, (19) 4- (4-benzylpiperidin-1-ylmethyl) nitrobenzene, (20) 4- (4-ethoxycarbonylpiperidin-1-ylmethyl) nitrobenzene, (21 ) 4- (K, No. dipropylaminomethyl) nitrobenzene, (22) 4- (4-tert-butoxycarbonylpiperazin-1-ylmethyl) nitrobenzene, (23) 4- (2-morpholin-4-ylethyl) nitrobenzene, (24) 4- (2-pyrrolidin-1-ylethyl) nitrobenzene, (25) 4- (2-piperidin-1-leethyl) nitrobenzene, (26) 4- (K-ethyl-N-benzylaminomethyl) nitrobenzene, (2 7) 4- (K-propyl-N-benzylaminomethyl) nitrobenzene, (28) 4- [N-methyl-M- (4-chlorobenzyl) aminomethyl] nitrobenzene, (29) 4- [N-methyl-M- (4 -bromobenzyl) aminomethyl] nitrobenzene, (30) 4- [N-methyl-M- (4-fluorobenzyl) aminomethyl] nitrobenzene, (31) 4- [N-methyl-M- (4-methylbenzyl) aminomethyl] nitrobenzene, ( 32) 4- [Ν -methyl-L- (3-chlorobenzyl) aminomethyl] nitrobenzene, (33) 4- [N-methyl-M- (3,4-dimethoxybenzyl) aminomethyl] nitrobenzene, (34) 4- [Ы -methyl-M- (4-methoxybenzyl) aminomethyl] nitrobenzene, (35) 4- (K-2,2,2-trifluoroethyl-N-benzylaminomethyl) nitrobenzene, (36) 4- [Y-2,2,2- trifluoroethyl-M- (4-chlorobenzyl) aminomethyl] nitrobenzene, (37) 4- (thiomorpho in-4-ylmethyl) nitrobenzene, (3 8) 4- (azetidione-1-methylmethyl) nitrobenzene, (3 9) 4- (3,4-dihydropyrrolidin-1-ylmethyl) nitrobenzene, (40) 4- (3, 4-dihydropiperidin-1-ylmethyl) nitrobenzene, (41) 4- (2-methoxycarbonylpyrrolidin-1-ylmethyl) nitrobenzene, (42) 4- (3,5-dimethylpiperidin-1-ylmethyl) nitrobenzene, (43) 4- ( 4-phenylpiperazin-1-ylmethyl) nitrobenzene, (44) 4- (4-phenyl-4-hydroxypiperidin-1-ylmethyl) nitrobenzene, (45) 4- [Y- (3,4,5-trimethoxybenzyl) -M- methylaminomethyl] nitrobenzene, (46) 4- [L- (3,4-dimethoxybenzyl) -M-ethylaminomethyl] nitrobenzene,

- 27 006080 (47) 4-Shch- (2,6-dichlorobenzyl) -Nomethyl) aminomethyl] nitrobenzene, (48) 4-Shch- (4-trifluoromethylbenzyl) -№methyl) aminomethyl] nitrobenzene, (49) 4- (C-benzyl-Noisopropylaminomethyl) nitrobenzene, (50) 4- (C-benzyl-Nt-butylaminomethyl) nitrobenzene, (51) 4- (TsSch-diisopropylaminomethyl) nitrobenzene , (53) 4- (2,3,4,5-tetrahydrobenzo (b) azepin-3-ylmethyl) nitrobenzene, (54) 4- (2,3-dihydro-isoindole-2-ylmethyl) nitrobenzene, (55) 4- (6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolin-2-ylmethyl) nitrobenzene, (56) 4- (1,2,3,4-tetrahydroisoquinolin-2-ylmethyl) nitrobenzene, (57) 4- Shch- (2-hydroxy yl) -Nbenzylaminomethyl] nitrobenzene, (58) 4-Shch- (1-ethylpentyl) -N (pyridin-2-ylmethyl) aminomethyl] nitrobenzene, (59) 4- (piperin-1 -ylmethyl) -1,3- dinitrobenzene, (60) 4- (C-phenethyl-methyl-aminomethyl) nitrobenzene, (61) 4- [Ν- (3 E-dihydroxyphenethyl) -Ν-methylaminomethyl]-nitrobenzene, (62) 4- [L- (3,4 , 5-trimethoxyphenmethyl) -M-methylaminomethyl] nitrobenzene, (63) 4- [L- (3,4-dimethoxyphenethyl) -M-methylaminomethyl] nitrobenzene, (64) 4- [L- (3,4-dimethoxybenzyl) - M-methylaminomethyl] nitrobenzene, (65) 4- [Ν- (4-chlorobenzyl) -Ν-methylaminomethyl] nitrobenzene, (66) 4-Shch- (4-bromobenzyl) -№methylaminomethyl] nitrobenzene, (67) 4-Shch - (4-fluoroben Il) -Nomethylaminomethyl] nitrobenzene, (68) 4-Shch- (4-methylbenzyl) -Nmethylaminomethyl] nitrobenzene, (69) 4- [Ν- (4-nitro phenethyl) ^ - methylaminomethyl] nitrobenzene, (70) 4 - (I-phenethyl-No. Benzylaminomethyl) nitrobenzene, (71) 4- (C-phenethyl-No. Cyclohexylaminomethyl) nitrobenzene, (72) 4-Sch- (2- (pyridin-2-yl) ethyl) -Nomethylaminomethyl] nitrobenzene , (73) 4-Sch- (2- (pyridin-4-yl) ethyl) -Nomethylaminomethyl] nitrobenzene, (74) 4- [Ν- (pyridin-4-ylmethyl) -Ν-methylaminomethyl] nitrobenzene, (75 ) 4- (TsShch-dibenzylaminomethyl) nitrobenzene, (76) 4-Shch- (4-nitrophenethyl) -N. propylaminomethyl] nitrobenzene, (77) 4- (K-benzyl-No. (3-cyanopropyl) aminomethyl ) nitrobenzene, (78) 4- (C-benzyl-No. allylaminomethyl) nitrobenzene, (79) 4-U-benzyl-No (2,2,2-trifluoroethyl) aminomethyl] nitrobenzene, (80) 4-U-2- (2 -benzo (1,3) dioxol-5-ylmethyl) -Nomethylaminomethyl] nitrobenzene, (81) 4- (7-chloro-2,3,4,5-tetrahydrobenzo (b) azepin-3-ylmethyl) nitrobenzene, ( 82) 4- (7,8-dichloro-2,3,4,5-tetrahydrobenzo (b) azepin-3-ylmethyl) nitrobenzene, (83) 4- (7-methoxy-2,3,4,5-tetrahydrobenzo (b) azepin-3-ylmethyl) nitrobenzene, (84) 4- (7-methyl-2,3,4,5-tetrahydrobenzo (b) azepin-3-ylmethyl) nitrobenzene, (85) 4- (7.8 -dimethoxy-2,3,4,5-tetrahydrobenzo (b) azepin-3-ylmethyl) nitrobenzene, (86) 4- (6,7-dichloro-1,2,3,4-tetrahydroisoquinol n-2-ylmethyl) nitrobenzene, (87) 4- (6,7-dimethyl-1,2,3,4-tetrahydroisoquinolin-2-ylmethyl) nitrobenzene, (88) 4- (6-chloro-1,2, 3,4-tetrahydroisoquinolin-2-ylmethyl) nitrobenzene, (89) 4- (7-chloro-1,2,3,4-tetrahydroisoquinolin-2-ylmethyl) nitrobenzene, (90) 4- (6-methoxy-1, 2,3,4-tetrahydroisoquinolin-2-ylmethyl) nitrobenzene, (91) 4- (7-methoxy-1,2,3,4-tetrahydroisoquinolin-2-ylmethyl) nitrobenzene, (92) 4 - [(2,3 , 4,5-tetrahydroazepino (4,5-b) pyrazin-3-yl) methyl] nitrobenzene, (93) 4 - [(7-amino-2,3,4,5-tetrahydroazepino (4,5-b) pyrazin-3-yl) methyl] nitrobenzene, (94) 4 - [(2-amino-5,6,7,8-tetrahydroazepino (4,5-b) thiazol-6-yl) methyl] nitrobenzene, (95) 4 - [(5,6,7,8-t etrahydroazepino (4,5-b) thiazol-6-yl) methyl] nitrobenzene.

Example XV. 4- (1,1-Dioxothiomorpholin-4-ylmethyl) nitrobenzene.

6.0 g of 4- (thiomorpholin-4-ylmethyl) nitrobenzene are dissolved in 100 ml of methylene chloride and 10.3 g of meta-chloroperbenzoic acid are slowly added. After stirring for 3 hours at room temperature, the precipitate is filtered off.

Yield: 6.2 g (91% of theory),

Purpose: 0.5 (silica gel, methylene chloride / methanol in a 1: 1 ratio),

C11 \ O% mass spectrum: t / ζ = 270 | M '].

Analogously to Example XV, the following compound is obtained:

(1) 4- (1-Oxothiomorpholin-4-ylmethyl) nitrobenzene.

Example XVI. 4- [Ν- (3- Aminopropyl) -Ν-methylsulfonylamino] nitrobenzene.

9.5 g of 4-Sch- (3-phthalimido-2-ylpropyl) -Mnomethylsulfonylamino] nitrobenzene are dissolved in 200 ml of ethanol, 11.5 ml of hydrazine hydrate is added and the mixture is stirred for 1.5 hours at 50 ° C. After cooling the residue is concentrated to almost dryness, water is added and the solution is extracted with methylene chloride. The organic phase is dried, concentrated and purified on a silica gel column using methylene chloride / methanol / ammonia 9: 1: 0.1.

Output: 2.5 g (39% of theory), ^ (- value: 0.2 (silica gel, methylene chloride / methanol 9: 1), ^C 10 ^H 15 ^ ^O 4 ^8, mass spectrum (E8C: t / ζ = 272 [M – H ^- ].

Analogously to example XVI, the following compound is obtained:

(1) 6- [No. (2-dimethylaminoethyl) -Nomethylsulfonylamino] -3-aminonitrobenzene: the compound is obtained from 6- [No. (2-dimethylaminoethyl) -Nomethylsulfonylamino] -3-phthalimido-2-ylnitrobenzene.

Example XVII. 4- (1-Methylimidazol-2-yl) nitrobenzene.

7.5 g of 4- (imidazol-2-yl) nitrobenzene are dissolved in 50 ml of dimethyl sulfoxide and 5.0 g of potassium tert-butylate are added at 0 ° C. After stirring for one hour at room temperature, 2.6 ml of methyl iodide are added dropwise and the mixture is stirred for one hour at room temperature. After that, the residue is poured into a mixture of ice water and the precipitate formed is suction filtered, washed with water and dried.

Yield: 6.1 g (76% of theory),

Purpose: 0.6 (silica gel, methylene chloride / methanol in a ratio of 10: 1), ν 186-187 ° C.

Analogously to example XVII receive the following compounds:

(1) 4- (1-ethylimidazol-2-yl) nitrobenzene: the compound is obtained from 4- (imidazol-2-yl) nitrobenzene and ethyl iodide;

(2) 4- (1-benzylimidazol-2-yl) nitrobenzene: this compound is obtained from 4- (imidazol-2yl) nitrobenzene and benzyl bromide.

Example XVIII. 4 - [(C- (2- (2-methoxyethoxy) ethyl) -Nomethylamino) methyl] nitrobenzene.

5.0 g of 4-methylaminomethylnitrobenzene is dissolved in 30 ml of dimethylformamide and 4.6 g of 2 (2-methoxyethoxy) ethyl chloride is added. After stirring for 6 hours at 100 ° C., the solvent is distilled off and the residue is dissolved in ethyl acetate. The organic phase is washed with water and dried over sodium sulfate. After distilling off the solvent, the residue is purified on a column of alumina (activity 2-3) using toluene / ethyl acetate 5: 1 as solvent.

Output: 2.3 g (29% of theory),

Purpose: 0.5 (aluminum oxide, toluene / ethyl acetate = 5: 1), ^C 13 ^H 2s№ ^O 4 Mass Spectrum (E8TS: m / ζ = 267 [M-H ^-].

Example XIX. 4- (No. ethyl-no-tert-butoxycarbonylaminomethyl) nitrobenzene.

2.2 g of 4- (ethylaminomethyl) nitrobenzene are dissolved in 50 ml of ethyl acetate and stirred for 30 minutes at room temperature with 2.6 g of di-tert-butyl dicarbonate (tert-butoxycarbonyl anhydride). Finally, the solution is washed with water and concentrated.

Yield: 3.4 g,

H _g value: 0.3 (silica gel, methylene chloride / methanol in a ratio of 50: 1), and: 85 ° C.

Analogously to example XIX, the following compounds are obtained:

(1) 4- [No. (4-chlorophenylmethyl) -N.t-butoxycarbonylaminomethyl] nitrobenzene, (2) 4- (No.t-butoxycarbonylaminomethyl) nitrobenzene, (3) 4- (No.cyclohexyl-No.t-butoxycarbonylaminomethyl) nitrobenzene ( 4) 4- (no. Isopropyl-no. T-butoxycarbonylaminomethyl) nitrobenzene, (5) 4- (no. Methyl-no. T-butoxycarbonylaminomethyl) nitrobenzene, (6) 4- (no. Propyl-no. Tert-butoxycarbonylaminomethyl) nitrobenzene, (7) 4- (No. butyl-No.t-butoxycarbonylaminomethyl) nitrobenzene, (8) 4- (No. of methoxycarbonylmethyl-No.t-butoxycarbonylaminomethyl) nitrobenzene, (9) 4- (No.benzyl-No.t-butoxycarbonylamino etil) nitrobenzene (10) 4- [№ (3-triftoratsetilaminopropil) -№metilsulfonilamino] nitrobenzene: the title compound was prepared from 4- [№ (3-aminopropyl) -№metilsulfonilamino] nitrobenzene and trifluoroacetic anhydride;

(11) 4 - [(4-tert-butoxycarbonylpiperazin-1-yl) methyl] nitrobenzene.

Example XX. 4- (Piperidin-1-ylmethyl) aniline.

37.0 g of 4- (piperidin-1-ylmethyl) nitrobenzene are dissolved in 300 ml of methanol, 8.0 g of Raney nickel are added and the mixture is hydrogenated for 85 min under 3 bar of hydrogen at room temperature. The catalyst is filtered off and the filtrate is evaporated.

Yield: 24.0 g (75% of theory),

H _g value: 0.4 (silica gel, methylene chloride / methanol in a ratio of 9: 1), ^C 12 ^H 18 ^N 2 ^,

- 29 006080 mass spectrum (EM): t / ζ = 191 [Ν + H ⁺ ].

Analogously to example XX, the following compounds are obtained:

(1) 4- [(2,6-dimethylpiperidin-1-yl) methyl] aniline, (2) No. (2-dimethylaminoethyl) -Nomethylsulfonyl-p-phenylenediamine, (3) 3- (dimethylaminomethyl) aniline, (4 ) 4- (dimethylaminomethyl) aniline, (5) 4- (2-dimethylaminoethyl) aniline, (6) 4- [no. (2-dimethylaminoethyl) -Nacetylamino] aniline, (7) 4- [no. (3-dimethylaminopropyl) -Noacetylamino] aniline, (8) 4- [No. (2-dimethylaminoethyl) -Nbenzoylamino] aniline, (9) 4- [No. (2-dimethylaminoethyl) -№propionylamino] aniline, (10) 4- [Ν- (2-dimethylaminoethyl) -Ν-butyrylamino] aniline, (11) 4- [H- (2-dimethylaminoethyl) -N isobutyrylamino] aniline, (12) 4- (C-tert-butoxycarbonylaminomethyl) aniline, (13) 4- ( -ethyl-No-tert-butoxycarbonylaminomethyl) aniline, (14) 4- [H- (4-chlorophenylmethyl) -No-tert-butoxycarbonylaminomethyl] aniline, (15) 4- (C-cyclohexyl-No. tert-butoxycarbonylaminomethyl) aniline, (16 ) 4- (C-isopropyl-N-tert-butoxycarbonylaminomethyl) aniline, (17) 4- (C-propyl-N-tert-butoxycarbonylaminomethyl) aniline, (18) 4- (C-methyl-N-tert-butoxycarbonylaminomethyl) aniline, ( 19) 4- (C-butyl-N-tert-butoxycarbonylaminomethyl) aniline, (20) 4- (C-methoxycarbonylmethyl-N-tert-butoxycarbonylaminomethyl) aniline, (21) 4- (C-benzyl-N-tert-butoxycarbonylaminomethyl) aniline, (22) 4- (pyrrolidin-1-ylmeti ) aniline, (23) 4- (morpholin-4-ylmethyl) aniline, (24) 4- (hexamethyleneimino) aniline, (25) 4- (4-hydroxypiperidin-1-ylmethyl) aniline, (26) 4- (4 -methoxypiperidin-1-ylmethyl) aniline, (27) 4- (4-methylpiperidin-1-ylmethyl) aniline, (28) 4- (4-ethylpiperidin-1-ylmethyl) aniline, (29) 4- (4-isopropylpiperidine -1-ylmethyl) aniline, (30) 4- (4-phenylpiperidin-1-ylmethyl) aniline, (31) 4- (4-benzylpiperidin-1-ylmethyl) aniline, (32) 4- (4-ethoxycarbonylpiperidin-1 -ylmethyl) aniline, (33) 4- (C, N, dipropylaminomethyl) aniline, (34) 4- (4-tert-butoxycarbonylpiperazin-1-ylmethyl) aniline, (35) 4- (2-morpholin-4-ylethyl) aniline, (36) 4- (2-pyrrolidin-1-ethyl ) aniline, (37) 4- (2-piperidin-1-leethyl) aniline, (3 8) 4- (No. propyl-No. benzylaminomethyl) aniline, (39) 4- [No. (n-hexyl) -№ methylaminomethyl] aniline, (40) 4- [Methyl-No (4-chlorobenzyl) aminomethyl] aniline, (41) 4 - ^ - methyl ^ - (4-bromobenzyl) aminomethyl | aniline.

(42) 4- [N-methyl-No. (4-methylbenzyl) aminomethyl] aniline, (43) 4- [N-methyl-No. (4-fluorobenzyl) aminomethyl] aniline, (44) 4- [N-methyl- No. (3-Chlorobenzyl) aminomethyl] aniline, (45) 4- [N-methyl-No. (3,4-dimethoxybenzyl) aminomethyl] aniline, (46) 4- [N-methyl-No. (4-methoxybenzyl) aminomethyl] aniline, (47) 4- (C-2,2,2-trifluoroethyl-Nbenzylaminomethyl) aniline, (48) 4- [H-2,2,2-trifluoroethyl-No (4-chlorobenzyl) aminomethyl] aniline, ( 49) 4- (thiomorpholin-4-ylmethyl) aniline, (50) 4- (1-oxiomorpholin-4-ylmethyl) aniline, (51) 4- (1,1-dioxothiomorpholin-4-ylmethyl) aniline, (52) 4- (azetidione-1 -ylmethyl) aniline, (53) 4- (3,4-dihydropyrrolidin-1-ylmethyl) aniline, (54) 4- (3,4-dig Droperidin-1-ylmethyl) aniline, (55) 4- (2-methoxycarbonylpyrrolidin-1-ylmethyl) aniline, (56) 4- (3,5-dimethylpiperidin-1-ylmethyl) aniline, (57) 4- (4- phenylpiperazin-1 -ylmethyl) aniline, (58) 4- (4-phenyl-4-hydroxypiperidin-1-ylmethyl) aniline, (59) 4- [No. (3,4,5-trimethoxybenzyl) -№methylaminomethyl] aniline, (60) 4- [No. (3,4-dimethoxybenzyl) -No-aminomethyl] aniline,

- 30 006080 (61) 4- (K-benzyl-N-ethylaminomethyl) aniline, (62) 4- [N- (2,6-dichlorobenzyl) -H-methylaminomethyl] aniline, (63) 4- [Ν- ( 4-trifluoromethylbenzyl) -Ν-methylaminomethyl] aniline, (64) 4- (K-benzyl-M-isopropylaminomethyl) aniline, (65) 4- (K-benzyl-N-tert-butylaminomethyl) aniline, (66) 4- (diethylaminomethyl) aniline, (67) 4- (2-diethylaminoethyl) aniline, (68) 4- (K, N-diisopropylaminomethyl) aniline, (69) 4- (K, N-diisobutylaminomethyl) aniline, (70) 4- (2,3,4,5-tetrahydrobenzo (phasepin-3-ylmethyl) aniline, (71) 4- (2,3-dihydroisoindol-2-ylmethyl) aniline, (72) 4- (6,7-dimethoxy-1 , 2,3,4-tetrahydroisoquinolin-2-ylmethyl) aniline, (73) 4- (1,2,3,4-tetrahydr isoquinolin-2-ylmethyl) aniline, (74) 4- [Ν- (2-hydroxyethyl) -Y-benzylaminomethyl] aniline, (75) 4- [L- (1-ethylpentyl) -H- (pyridin-2-ylmethyl ) aminomethyl] aniline, (76) 4- (piperidin-1 -ylmethyl) -3 -nitroaniline, (77) 4- (piperidin-1 -ylmethyl) -3-aminoaniline, (78) 4- (L-benzyl-M -methylaminomethyl) aniline, (79) 4- (L-ethyl-M-methylaminomethyl) aniline, (80) 4- (L-phenethyl-M-methylaminomethyl) aniline, (81) 4- [L- (3,4- dihydroxyphenethyl) -M-methylaminomethyl] aniline, (82) 4- [L- (3,4,5-trimethoxyphenethyl) -M-methylaminomethyl] aniline, (83) 4- [L- (3,4-dimethoxyphenethyl) -M -methylaminomethyl] aniline, (84) 4- [Y- (3,4-dimethoxybenzyl) -M-methylaminomethyl] an ling, (85) 4- [Ν- (4-chlorobenzyl) -Ν-methylaminomethyl] aniline, (86) 4- [L- (4-bromobenzyl) -M-methylaminomethyl] aniline, (87) 4- [L- (4-fluorobenzyl) -M-methylaminomethyl] aniline, (88) 4- [Ν- (4-methylbenzyl) -Ν-methylaminomethyl] aniline, (89) 4- [L- (4-nitrophenetil) -M-methylaminomethyl] aniline, (90) 4- (L-phenethyl-M-benzylaminomethyl) aniline, (91) 4- (L-phenethyl-M-cyclohexylaminomethyl) aniline, (92) 4- [L- (2- (pyridine-2- yl) ethyl) -M-methylaminomethyl] aniline, (93) 4- [L- (2- (pyridin-4-yl) ethyl) -M-methylaminomethyl] aniline, (94) 4- [L- (pyridine-4 -ylmethyl) -M-methylaminomethyl] aniline, (95) 4- (S, M-dibenzylaminomethyl) aniline, (96) 4- [M- (4-nitrobenzyl) -M-pro pilaminomethyl] aniline, (97) 4- [L-benzyl-H- (3-cyanopropyl) aminomethyl] aniline, (98) 4- (L-benzyl-M-allylaminomethyl) aniline, (99) 4- [L-benzyl -M- (2,2,2-trifluoroethyl) aminomethyl] aniline, (100) 4 - [(benzo (1,3) dioxol-5-ylmethyl) methylaminomethyl] aniline, (101) 4- (7-chloro-2 3,4,5-tetrahydrobenzo (phasepin-3-ylmethyl) aniline, (102) 4- (7,8-dichloro-2,3,4,5-tetrahydrobenzo (phasepin-3-ylmethyl) aniline, (103) 4- (7-methoxy-2,3,4,5-tetrahydrobenzo (phasepin-3-ylmethyl) aniline, (104) 4- (7-methyl-2,3,4,5-tetrahydrobenzo (phasepin-3-ylmethyl ) aniline, (105) 4- (7,8-dimethoxy-2,3,4,5-tetrahydrobenzo (phasein-3-ylmethyl) aniline, (106) 4- (6,7-dichloro-1,2,3 , 4-tetrahydr isoquinolin-2-ylmethyl) aniline, (107) 4- (6,7-dimethyl-1,2,3,4-tetrahydroisoquinolin-2-ylmethyl) aniline, (108) 4- (6-chloro-1,2, 3,4-tetrahydroisoquinolin-2-ylmethyl) aniline, (109) 4- (7-chloro-1,2,3,4-tetrahydroisoquinolin-2-ylmethyl) aniline, (110) 4- (6-methoxy-1, 2,3,4-tetrahydroisoquinolin-2-ylmethyl) aniline, (111) 4- (7-methoxy-1,2,3,4-tetrahydroisoquinolin-2-ylmethyl) aniline, (112) 4- (2,3, 4,5-tetrahydroazepino (4,5-b) pyrazin-3-ylmethyl) aniline, (113) 4- (7-amino-2,3,4,5-tetrahydroazepino (4,5-b) pyrazin-3- ylmethyl) aniline, (114) 4- (2-amino-5,6,7,8-tetrahydroazepino (4,5-phthiazol-6-ylmethyl) aniline, (115) 4- (5,6,7,8- tetrahydroazepino (4,5-phthiazol-6-ylmethyl) nilin, (116) 4- (4-methylpiperazin-1-yl) aniline, (117) 4- [L- (2-dimethylaminoethyl) -H-methylamino] aniline, (118) 4- [L- (3-dimethylaminopropyl ) -N-methylamino] aniline, (119) N- (3-dimethylaminopropyl) -N-methylsulfonyl-p-phenylenediamine, (120) 4 - [(N-dimethylaminocarbonylmethyl-N-methylsulfonyl) amino] aniline, (121) - (4-amino-phenyl) -Ν-methylmethanesulfonamide, (122) 4- (imidazol-4-yl) aniline,

- 31 006080 (123) 4- (tetrazol-5-yl) aniline, (124) 4- [L- (2-dimethylaminoethyl) -H-propionylamino] aniline, (125)-(dimethylaminomethylcarbonyl) -Ν-methyl- p-phenylenediamine, (126) No. [(2-dimethylaminoethyl) carbonyl] -Y-methyl-p-phenylenediamine, (127) 4- (No. acetyl-I-dimethylaminocarbonylmethyl) amino) aniline, (128) N-methylaminocarbonylmethyl-N -methylsulfonyl-p-phenylenediamine, (129) N-aminocarbonylmethyl-N-methylsulfonyl-p-phenylenediamine, (130) 4- (imidazolidin-2,4-dione-5-ylidenemethyl) aniline, (131) 4- (imidazolidine- 2,4-Dione-5-ylmethyl) aniline, (132) 4- (2-oxopyrrolidin-1-ylmethyl) aniline, (133) N-cyanomethyl-N-methylsulfony -p-phenylenediamine, (134) 4- [2- (imidazol-4-yl) ethyl] aniline, (135) 4 - [(4-methylpiperazin-1-yl) methyl] aniline, (136) 4- [No. (2- (No.Benzyl-N-methylamino) ethyl) -N-methylsulfonylamino] aniline, (137) 4- [No. (3- (No.Benzyl-N-methylamino) propyl) -Y-methylsulfonylamino] aniline, (138) -Cyclohexyl-p-phenylenediamine, (139) 4- (pyridin-4-ylmethyl) aniline, (140) 4- (imidazol-1-ylmethyl) aniline, (141) 4-benzylaniline, (142) no. (3- trifluoroacetylaminopropyl) -Y-methylsulfonyl-p-phenylenediamine, (143) 4-aminophenylacetic acid t-butyl ester, (144) 4- (imidazol-2-yl) aniline, (145) 4- (1-methyl-imidazol-2-yl ) aniline, (146) 4- (1-ethylimidazol-2-yl) an Lin, (147) 4- (1-benzylimidazol-2-yl) aniline, (148) 4- [No. (2-dimethylaminoethyl) -Y-methylsulfonylamino] -3-aminoaniline, (149) 4- [L- (2 -dimethylaminoethyl) -N-methylsulfonylamino] -3-chloroaniline, (150) 4- [No. (2-dimethylaminoethyl) -Y-acetylamino] -3-aminoaniline, (151) 4- [L- (2-dimethylaminoethyl) -H -acetylamino] -3-bromoaniline, (152) 4- [2- (4-hydroxypiperidin-1-yl) ethylamino] aniline, (153) No. (2-dimethylaminoethyl) -Y-ethylsulfonyl-p-phenylenediamine, (154) No. (2-dimethylaminoethyl) -Y-propylsulfonyl-p-phenylenediamine, (155) No. (2-dimethylaminoethyl) -Y-isopropylsulfonyl-p-phenylenediamine, (156) No. (2-dimethylaminoethyl) -Y-butylsulf nyl-p-phenylenediamine, (157) No. (2-dimethylaminoethyl) -Y-benzylsulfonyl-p-phenylenediamine, (158) No. (2-dimethylaminoethyl) -Y-phenylsulfonyl-p-phenylenediamine, (159) 4 - ((3 α-hydroxypyrrolidin-1-yl) methyl) aniline, (160) 4- [No. (2-dimethylaminoethyl) -H- (furan-2-carbonyl) amino] aniline, (161) 4- [L- (2-dimethylaminoethyl) -H- (2-methoxybenzoyl) amino] aniline, (162) 4- [L- (2-dimethylaminoethyl) -H- (pyridine-3-carbonyl) amino] aniline, (163) 4- [L- (2- dimethylaminoethyl) -N- (phenylacetyl) amino] aniline, (164) N- (piperidin-1-methylmethylcarbonyl) -Y-methyl-p-phenylenediamine, (165) No. (morpholine-4-ylmethylcarbonyl) -Y-methyl-n -phenylenediamine, (166) No. [(4-b Enzylpiperazin-1-yl) methylcarbonyl] -Y-methyl-p-phenylenediamine, (167) No. (pyrrolidin-1-ylmethylcarbonyl) -Y-methyl-p-phenylenediamine, (168) 4- (5-methylimidazol-4-yl ) aniline, (169) No. [(2-dimethylaminoethyl) carbonyl] -Y-isopropyl-p-phenylenediamine, (170) No. [(2-dimethylaminoethyl) carbonyl] -Y-benzyl-p-phenylenediamine, (171) No. ( K-aminocarbonylmethyl-N-methylamino) methylcarbonyl) -Y-methyl-p-phenylenediamine, (172) No. [(K-benzyl-N-methylamino) methylcarbonyl] -Y-methyl-p-phenylenediamine, (173) No. [di - (2-methoxyethyl) aminomethylcarbonyl] -Y-methyl-p-phenylenediamine, (174) No. [(2- (4-tert-butoxycarbonylpiperazin-1-yl) ethyl) carb onyl] -Y-methyl-p-phenylenediamine, (175) No. [(2- (piperidin-1-yl) ethyl) carbonyl] -Y-methyl-p-phenylenediamine, (176) No. [(2- (No. benzyl -H-methylamino) ethyl) carbonyl] -Y-methyl-p-phenylenediamine, (177) No. (dimethylaminomethylcarbonyl) -Y-isopropyl-p-phenylenediamine, (178) No. (piperidine-1-ylmethylcarbonyl) -Y-isopropyl- p-phenylenediamine, (179) No. [(4-tert-butoxycarbonylpiperazin-1-yl) methylcarbonyl] -Y-isopropyl-p-phenylenediamine, (180) No. [(K-benzyl-N-methylamino) methylcarbonyl] -Y- benzyl-p-phenylenediamine, (181) No. (dimethylaminomethylcarbonyl) -Y-benzyl-p-phenylenediamine, (182) Ν- (piperidine-1 -ylmethylcarbonyl) -Ν-benzyl -p-phenylenediamine, (183) 4- (1,2,4-triazol-1 -ylmethyl) aniline, (184) 4- (1,2,3-triazol-2-ylmethyl) aniline,

- 32 006080 (185) 4- (1,2,3-triazol-1-methylmethyl) aniline, (186) 4- [(Ethoxycarbonylmethyl-Nomethylamino) methyl] aniline, (187) 4 - [(No. of aminocarbonylmethyl- No.methylamino) methyl] aniline, (188) 4- (azetidin-1-ylmethyl) aniline, (189) 4 - [(di- (2-methoxyethyl) amino) methyl] aniline, (190) 4 - [(no ( 2- (2-methoxyethoxy) ethyl) -Nomethylamino) methyl] aniline, (191) 4- [No. (No. of tert-butoxycarbonyl-3-aminopropyl) -№methylaminomethyl] aniline, (192) 4 - [(No. (methylcarbamoylmethyl ) -№methylamino) methyl] aniline, (193) 4 - [(no. (Dimethylcarbamoylmethyl) -Nomethylamino) methyl] aniline, (194) 4- [(No.propyl-nomethylamino) methyl] aniline, (195) 4- [(No. (2-dimethylaminoethyl) -methyl foreign) methyl] aniline, (196) 4 - [(no. (3-dimethylaminopropyl) -Nomethylamino) methyl] aniline, (197) 4- [(no. (2-methoxyethyl) -№methylamino) methyl] aniline, (198 ) 4 - [(no. (2-hydroxyethyl) -Nomethylamino) methyl] aniline, (199) 4 - [(no. (Dioxolan-2-ylmethyl) -Nomethylamino) methyl] aniline, (200) 4- (3 - oxopiperazin-1-methylmethyl) aniline, (201) No. [di (2-hydroxyethyl) aminomethylcarbonyl] -Nomethyl-p-phenylenediamine, (202) No. [(No. (2-methoxyethyl) -Mmethylamino) methylcarbonyl] -№methyl -p-phenylenediamine, (203) No. [(No. (2-dimethylaminoethyl) -Nomethylamino) methylcarbonyl] -Mn.-methyl-p-phenylenediamine, (204) No. [(4-methyl-piperazin-1-yl) methylcarbonyl] -№methyl p-feni endiamin (205) № [(imidazol-1-yl) methylcarbonyl] -№metil-p-phenylenediamine, (206) № [(phthalimido-2-yl) methylcarbonyl] -№metil-p-phenylenediamine.

Example XXI. 4- (4-Hydroxymethylpiperidin-1-ylmethylamino) aniline.

1.1 g of 4- (4-ethoxycarbonylpiperidin-1-ylmethylamino) aniline is suspended in 15 ml of tetrahydrofuran. 175 mg of lithium borohydride are added at room temperature, stirred for 24 hours, 175 mg of lithium borohydride are added again and after 7.5 hours, 15 ml of water are added and stirred for 10 minutes. Then extracted three times with ethyl acetate in portions of 15 ml. The combined organic phases are washed with water and saturated saline solution, dried over sodium sulfate and evaporated on a rotary evaporator. The residue is purified on a silica gel column using methylene chloride / methanol / ammonia mixture as a solvent in a ratio of 4: 1: 0.01.

Yield: 200 mg (27% of theory),

Purpose: 0.4 (silica gel, methylene chloride / methanol / ammonia in the ratio 4: 1: 0.01),

V 157 ° C.

Example XXII. Methyl 4-methoxycarbonylmethyl-3-nitrobenzoic acid.

54.3 g of 3-nitrobenzoic acid methyl ester and 29.0 g of chloroacetic acid methyl ester are dissolved in 100 ml of dimethylformamide and this solution is added dropwise at -10 ° C to the solution

78.5 g of potassium t-butoxide in 500 ml of dimethylformamide. Next, the mixture is stirred for 10 minutes at room temperature and then the solution is poured into 350 ml of concentrated hydrochloric acid in 2 l of ice-water. Then the solution is stirred for 0.5 h, the precipitate obtained is suction filtered and washed with water. The product is recrystallized from 150 ml of methanol and dried in vacuum at 40 ° C.

Output: 48.3 g (51% of theory), contains about 20% of methyl ester of 6-methoxycarbonylmethyl-3 nitrobenzoic acid,

H (-value: 0.7 (silica gel, petroleum ether / ethyl acetate 1: 1), and: 65-73 ° C.

Analogously to example XXII receive the following connection:

(1) 4-methoxycarbonylmethyl-3-nitrobenzoic acid ethyl ester: this compound is obtained from 3-nitrobenzoic acid ethyl ester.

Example XXIII Methyl ester of 2-indolinone-6-carboxylic acid.

48.3 g of 4-methoxycarbonylmethyl-3-nitrobenzoic acid methyl ester is dissolved in 800 ml of concentrated acetic acid, 5.0 g of palladium on carbon (10%) are added and the solution is hydrogenated for 2.5 hours at room temperature and 50 pounds of pressure / sq. inch Next, the catalyst is filtered off and the filtrate is evaporated. The residue is dissolved in 150 ml of tert-butyl methyl ether, filtered again and dried under vacuum at 100 ° C.

Output: 28.6 g (98% of theory),

H (-value: 0.4 (silica gel, methylene chloride / methanol 10: 1), ν 208-211 ° C.

Analogously to example XXIII receive the following connection:

(1) 2-Indolinone-6-carboxylic acid ethyl ester: the compound is obtained from 4-methoxycarbonylmethyl-3-nitrobenzoic acid ethyl ester.

Example XXIV. 1-Acetyl-3 - (1-ethoxy-1-phenylmethylene) -6-ethoxycarbonyl-2-indolinone.

- 33 006080

15.0 g of 2-indolinone-6-carboxylic acid ethyl ester, 49.6 ml of orthobenzoic acid triethyl ester and 150 ml of acetic anhydride are stirred for 4 hours at 110 ° C. After that, the solvent is distilled off, the residue is recrystallized from petroleum ether and dried in vacuum at 50 ° C.

Yield: 16.9 g (61% of theory),

In _g value: 0.5 (silica gel, petroleum ether / methylene chloride / acetic ether in the ratio 5: 4: 1),

1 ™: 98-100 ° C

C22H2 ^ O5.

Analogously to example XXIV receive the following compounds:

(1) 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-methoxycarbonyl-2-indolinone: this compound is obtained from 2-indolinone-6-carboxylic acid methyl ester, ortho-benzoic acid triethyl ester and acetic acid anhydride;

(2) 1-acetyl-3- (1-ethoxy-1-ethylmethylene) -6-ethoxycarbonyl-2-indolinone: this compound is obtained from 2-indolinone-6-carboxylic acid ethyl ester, ortho-propionic acid ethyl ester and acetic anhydride.

Obtaining final compounds

Example 1. Trifluoroacetate 3-2- [1- (4- (piperidin-1-ylmethyl) anilino) -1-phenylmethylene] -6-carbamoyl-2-indolinone.

300 mg of the resin obtained according to Example II is suspended in 3 ml of dimethylformamide and shaken with 0.2 g of 4- (piperidin-1-ylmethyl) aniline for 22 hours at 70 ° C. After that, the mixture is filtered and the resin is washed several times with methylene chloride, methanol and dimethylformamide. Next, to remove the acetyl group, 1 ml of methanolic ammonia solution is added over 2 hours. Finally, after repeated washing, 4 ml of 10% trifluoroacetic acid in methylene chloride are added over 60 minutes, the resin is separated and the solution is concentrated.

Yield: 69 mg,

In _g value: 0.1 (silica gel, methylene chloride / methanol in the ratio 9: 1), ^C 28 ^Η 28 ^N 4 ^O 2 ^, mass spectrum: t / = 452 (M ').

Analogously to example 1, the following compounds are obtained:

(1) 3-2- (1-anilino-1-phenylmethylene) -6-carbamoyl-2-indolinone: the compound is obtained from the obtained resin according to Example II and aniline, ^C 22 ^H 17 ^ ^O 2, mass spectrum: t / ζ = 355 (M ');

(2) 3-Ζ- [1- (4-dimethylaminomethylanilino) -1-phenylmethylene] -6-carbamoyl-2-indolinone trifluoroacetate: the compound was obtained from the resin obtained according to example II and 4dimethylaminomethylaniline, ^C 25 ^Η 24 ^N 4 ^O 2 ^, mass spectrum: t / ζ = 412 (M ');

(3) 3-Ζ- [1- (4- (2-diethylaminoethyl) anilino) -1-phenylmethylene] -6-carbamoyl-2-indolinone trifluoroacetate: the compound was obtained from the resin prepared according to Example II and 4- (2-diethylaminoethyl) aniline, ^C 28 ^Η 30 ^N 4 ^O 2 ^, mass spectrum: t / ζ = 454 (M ⁺ );

(4) 3 -Ζ- [1- (4- (morpholin-4-ylmethyl) anilino) -1-phenylmethylene] -6-carbamoyl-2-indolinone trifluoroacetate 3: the compound obtained is obtained from the resin obtained according to example II and 4- ( morpholine-4ylmethyl) aniline,

In _g value: 0.50 (silica gel, methylene chloride / methanol in the ratio 4: 1), ^C 27 ^Η 26 ^N 4 ^O 3 ^, mass spectrum: t / = 454 (M ⁺ );

(5) 3-Ζ- [1- (4- (1-oxothiomorpholin-4-ylmethyl) anilino) -1-phenylmethylene] -6-carbamoyl-2-indolinone trifluoroacetate 3: the compound obtained is obtained from the resin prepared according to example II and 4 - (1oxothiomorpholin-4-ylmethyl) aniline,

B-value: 0.30 (silica gel, methylene chloride / methanol 9: 1),

C27H26 ^ Oe8, mass spectrum: t / ζ = 486 (M ⁺ );

(6) 3-Ζ- [1- (4- (1,1-dioxothiomorpholin-4-ylmethyl) anilino) -1-phenylmethylene] -6carbamoyl-2-indolinone trifluoroacetate: the compound is obtained from the resin prepared according to example II and 4 - (1,1-dioxothiomorpholin-4-ylmethyl) aniline,

The _r value: 0.30 (silica gel, methylene chloride / methanol 9: 1), 27 ^C ^Η 26 ^N 4 ^O ⁴⁸ MS: m / ζ = 502 (M ^+);

- 34 006080 (7) trifluoroacetate 3 ^ - [1- (4- (benzylaminomethyl) anilino) -1-phenylmethylene] -6-carbamoyl-2-indolinone: the compound is obtained from the resin obtained according to example II and 4- [K ( phenylmethyl) nt-butoxycarbonylaminomethyl] aniline,

K _g value: 0.40 (silica gel, methylene chloride / methanol in the ratio 4: 1), ^C 30 ^Η 26 ^N 4 ^O 2 ^, mass spectrum: t / = 474 (M ⁺ );

(8) 3 -Ζ- [1- (4- (aminomethyl) anilino) -1-phenylmethylene] -6-carbamoyl-2-indolinone trifluoroacetate: the compound obtained is obtained from the resin prepared according to example II and 4- (Ctretbutoxycarbonylaminomethyl) aniline,

K-value: 0.10 (silica gel, methylene chloride / methanol in the ratio 4: 1), ^C 23 ^Η 20 ^N 4 ^O 2 ^, mass spectrum: t / = 384 (M ⁺ );

(9) 3-тора- [1 - (4- (2,6-dimethylpiperidin-1-ylmethyl) anilino) -1-phenylmethylene] -6-carbamoyl-2-indolinone trifluoroacetate: the compound was obtained from the resin obtained according to example II and 4- (2,6 dimethylpiperidin-1-ylmethyl) aniline,

K _g value: 0.45 (silica gel, methylene chloride / methanol in the ratio 4: 1), ^ 0 ^ 2 ^ ¾ mass spectrum: t / ζ = 480 (M ⁺ );

(10) 3 -Ζ- [1 - (4- (pyrrolidin-1-ylmethyl) anilino) -1-phenylmethylene] -6-carbamoyl-2indolinone trifluoroacetate: the compound was obtained from the resin obtained in Example II and 4 (pyrrolidin-1 -methyl) aniline,

K-value: 0.15 (silica gel, methylene chloride / methanol in the ratio 4: 1), ^C 27 ^Η 26 ^N 4 ^O 2 ^, mass spectrum: t / = 438 (M ⁺ );

(11) trifluoroacetate 3 ^ - [1- (3- (dimethylaminomethyl) anilino) -1-phenylmethylene] -6-carbamoyl-2-indolinone: the compound was obtained from the resin obtained according to example II and 3-dimethylaminomethylaniline,

K _g value: 0.23 (silica gel, methylene chloride / methanol in the ratio 4: 1), ^C 25 ^Η 24 ^N 4 ^O 2 ^, mass spectrum: t / = 412 (M ⁺ );

(12) 3 ^ - [1- (3- (Kmethyl-Kethylaminomethyl) anilino) -1-phenylmethylene] -6-carbamoyl-2-indolinone trifluoroacetate: the compound obtained from the resin prepared according to Example II and 3- (Kmethyl-ethylaminomethyl) aniline ,

Kg value: 0.23 (silica gel, methylene chloride / methanol in the ratio 4: 1), ^C 26 ^Η 26 ^N 4 ^O 2 ^, mass spectrum: t / = 426 (M ⁺ );

(13) 3-Ζ- [1- (3- (methylaminomethyl) anilino) -1-phenylmethylene] -6-carbamoyl-2-indolinone trifluoroacetate: the compound was obtained from the resin prepared according to Example II and 4- (Ctretbutoxycarbonyl-Kmethylaminomethyl) aniline,

K _g value: 0.06 (silica gel, methylene chloride / methanol in the ratio 4: 1), ^C 24 ^Η 22 ^N 4 ^O 2 ^, mass spectrum: t / = 399 (M + H ⁺ );

(14) 3 ^ - [1- (3-hydroxymethylanilino) -1-phenylmethylene] -6-carbamoyl-2-indolinone: the compound is obtained from the resin obtained according to Example II and 3-aminobenzyl alcohol,

Kg value: 0.7 (silica gel, methylene chloride / methanol in the ratio 4: 1), (USS, mass spectrum: t / ζ = 385 (M ⁺ );

(15) Trifluoroacetate 3 -Ζ- [1- (4- (methoxycarbonylmethylaminomethyl) anilino) -1-phenylmethylene] -6carbamoyl-2-indolinone: the compound obtained is obtained from the obtained according to example II resin and 4- (Kmethoxycarbonylmethyl-N-tert-butoxycarbonylaminomethyl) ) aniline,

K _g value: 0.40 (silica gel, methylene chloride / methanol in the ratio 9: 1), ^C 26 ^H 24 ^N 4 ^O 4 ^, mass spectrum: t / ζ = 457 (M + H ⁺ );

(16) 3 -Ζ- [1- (4- (Kmethylsulfonyl-K (dimethylaminocarbonylmethyl) amino) anilino) -1-phenylmethylene] -6-carbamoyl-2-indolinone: the compound was obtained from the resin obtained according to Example II and 4- (Cmethylsulfonyl-K (dimethylaminocarbonylmethyl) amino) aniline,

Kg value: 0.40 (silica gel, methylene chloride / methanol 9: 1),

CE-K-K ⁰ ^ mass spectrum: t / ζ = 533 (M ⁺ );

(17) 3 -Ζ- [1- (4- (Cacetylaminomethyl) anilino) -1-phenylmethylene] -6-carbamoyl-2-indolinone: the compound was obtained from the resin obtained according to Example II and 4- (α-acetylaminomethyl) aniline,

To _g value: 0,70 (silica gel, methylene chloride / methanol in the ratio 4: 1),

- 35 006080 ^С 25 ^Η 22 ^N 4 ^О 3 ^, mass spectrum: t / ζ = 426 (M ⁺ );

(18) 3-2- [1- (3,4-dimethoxyanilino) -1-phenylmethylene] -6-carbamoyl-2-indolinone: the compound is obtained from the resin obtained according to example II and 3,4-dimethoxyaniline,

K-value: 0.40 (silica gel, methylene chloride / methanol in a ratio of 9: 1), mass spectrum: t / ζ = 415 (M ⁺ );

(19) 3 -Ζ- [1- (4- (morpholin-4-yl) anilino) -1-phenylmethylene] -6-carbamoyl-2-indolinone trifluoroacetate: the compound was obtained from the resin prepared according to Example II and 4-morpholine -4ilaniline,

K-value: 0.20 (silica gel, methylene chloride / methanol 9: 1), 26 ^C ^Η 24 ^N 4 ^O ³ MS: m / ζ = 440 (M ^+);

(20) 3 ^ - [1- (4-acetylaminoanino) -1-phenylmethylene] -6-carbamoyl-2-indolinone: the compound is obtained from the resin obtained according to example II and 4-acetylaminoaniline,

K-value: 0.25 (silica gel, methylene chloride / methanol in the ratio 9: 1), ^C 24 ^Η 20 ^N 4 ^O 3 ^, mass spectrum: t / = 412 (M ⁺ );

(21) 3 ^ - [1- (4-aminoanilino) -1-phenylmethylene] -6-carbamoyl-2-indolinone: the compound is obtained from the resin obtained according to example II and 4-aminoaniline,

K-value: 0.40 (silica gel, methylene chloride / methanol in the ratio 9: 1), ^C 22 ^H 1 BW ^O 2, mass spectrum: t / ζ = 370 (M ⁺ );

(22) 3 -Ζ- [1 - (4-No.methyl-No.acetylaminoanilino) -1-phenylmethylene] -6-carbamoyl-2-indolinone: the compound was obtained from the resin obtained according to example II and 4-Sh-methyl-No. acetylamino) aniline, ^C 25 ^Η 22 ^N 4 ^O 3 ^, mass spectrum: t / ζ = 426 (M ⁺ );

(23) 3 ^ - [1- (4-ethoxycarbonylanilino) -1-phenylmethylene] -6-carbamoyl-2-indolinone: the compound is obtained from the resin obtained according to example II and 4-aminobenzoic acid ethyl ester, ^C 25 ^H 21 ^ ^O 4, mass spectrum: t / ζ = 427 (M ⁺ );

(24) 3 ^ - [1- (4-carboxyanilino) -1-phenylmethylene] -6-carbamoyl-2-indolinone: the compound is obtained from the resin obtained according to Example II and 4-aminobenzoic acid,

K-value: 0.11 (silica gel, methylene chloride / methanol in a ratio of 9: 1), ^C 23 ^H 17 ^ ^O 4, mass spectrum: t / 8 = 398 (M – H ⁺ );

(25) 3 -Ζ- [1- (4-benzylcarbamoylanilino) -1-phenylmethylene] -6-carbamoyl-2-indolinone: the compound is obtained from the resin obtained according to example II and 4-aminobenzoic acid benzylamide,

K-value: 0.21 (silica gel, methylene chloride / methanol 9: 1),

C30H24CHO3, mass spectrum: t / ζ = 488 (M ⁺ );

(26) 3 ^ - [1- (cyclohexylamino) -1-phenylmethylene] -6-carbamoyl-2-indolinone: the compound is obtained from the resin obtained according to example II and cyclohexylamine,

K-value: 0.60 (silica gel, methylene chloride / methanol 9: 1), ^C 22 ^H 23 ^ ^O 2>

mass spectrum: t / ζ = 361 (M ⁺ );

(27) trifluoroacetate 3 -Ζ- [1- (4-aminocyclohexylamino) -1-phenylmethylene] -6-carbamoyl-2-indolinone: the compound was obtained from the resin obtained according to example II and 4-amino cyclohexylamine, ^C 22 ^N 24 ScH ^O 2 , mass spectrum: t / ζ = 376 (M ⁺ );

(28) 3-Ζ- [1-Щ-methyl-piperidin-4-ylamino) -1-phenylmethylene] -6-carbamoyl-2-indolinone trifluoroacetate: the compound was obtained from the resin obtained according to example II and 4-amino-1-methylpiperidine,

K-value: 0.15 (silica gel, methylene chloride / methanol in the ratio 4: 1), ^C 22 ^H 24-No.4 ^O 2?

mass spectrum: t / ζ = 376 (M ⁺ );

- 36 006080 (29) trifluoroacetate 3 -Ζ- [1- (4- (piperidin-1-ylmethyl) anilino) -1-methylmethylene] -6-carbamoyl-2 indolinone: the specified compound is obtained from the resin obtained according to example P (2) and 4 (piperidin-1-ylmethyl) aniline,

K _d value: 0.30 (silica gel, methylene chloride / methanol = 4: 1), 23 ^C ^Η 26 ^N 4 ^O ² MS: m / ζ = 390 (M ^4);

(30) trifluoroacetate 3 -Ζ- [1- (3-dimethylaminomethylanilino) -1-methylmethylene] -6-carbamoyl-2-indolinone: the compound is obtained from the resin obtained according to example P (2) and 3-dimethylaminomethylaniline,

K-value: 0.51 (silica gel, methylene chloride / methanol in the ratio 4: 1), ^C 20 ^Η 22 ^N 4 ^O 2 ^, mass spectrum: t / = 351 (M + H ⁺ );

(31) trifluoroacetate 3 ^ - [1- (4- (#methyl-S-benzylaminomethyl) anilino) -1-methylmethylene] -6-carbamoyl-2-indolinone: the compound is obtained from the resin obtained according to example P (2) and 4- (methyl-Y-benzylaminomethyl) aniline,

K _g value: 0.73 (silica gel, methylene chloride / methanol 4: 1 ratio), ^C 26 ^Η 26 ^N 4 ^O 2 ^, mass spectrum: t / = 426 (M ');

(32) trifluoroacetate 3 ^ - [1- (4- (#methylsulfonyl-N- (2-dimethylaminoethyl) amino) anilino) -1-methylmethylene] -6-carbamoyl-2-indolinone: the compound obtained is obtained from obtained according to example P (2) resins and 4- (No. methylsulfonyl-L- (2-dimethylaminoethyl) amino) aniline,

C22H27 ^ O4§, mass spectrum: t / ζ = 458 (M + H ⁺ );

(33) 3 ^ - [1- (4-chloroanilino) -1-methylmethylene] -6-carbamoyl-2-indolinone: the compound is obtained from the resin obtained according to example P (2) and 4-chloroaniline,

K _g value: 0.10 (silica gel, methylene chloride / methanol in the ratio 9: 1), ^C 17 ^Η 14 ^C 1 ^N 3 ^O 2 ^, mass spectrum: t / 327 = 327/329 (M ⁴ );

(34) 3 ^ - [1- (3-chloroanilino) -1-methylmethylene] -6-carbamoyl-2-indolinone: the compound is obtained from the resin obtained according to example P (2) and 3-chloroaniline,

Kg value: 0.11 (silica gel, methylene chloride / methanol 9: 1),

C17H _AND SSh3O2, mass spectrum: t / ζ = 327/329 (M ⁴ );

(35) 3 ^ - [1- (4-methoxycarbonylanilino) -1-methylmethylene] -6-carbamoyl-2-indolinone: the compound is obtained from the resin obtained according to example P (2) and 4-aminobenzoic acid methyl ester,

K _g value: 0.11 (silica gel, methylene chloride / methanol in the ratio 9: 1), ^C 19 ^Η 17 ^N 3 ^O 4 ^, mass spectrum: t / = 351 (M ⁴ );

(36) 3 ^ - [1- (4-carboxyanilino) -1-methylmethylene] -6-carbamoyl-2-indolinone: the compound is obtained from the resin obtained according to example P (2) and 4-aminobenzoic acid, mass spectrum: t / ζ = 336 (M-H ⁺ );

(37) 3 ^ - [1- (4-methyl-3-nitroanilino) -1-methylmethylene] -6-carbamoyl-2-indolinone: the compound is obtained from the resin obtained according to example P (2) and 4-methyl-3 -nitroaniline,

Kg value: 0.82 (silica gel, methylene chloride / methanol in the ratio 4: 1), ^C 18 ^Η 16 ^N 4 ^O 4 ^, mass spectrum: t / ζ = 352 (M ⁴ );

(3 8) trifluoroacetate 3 -Ζ- [1- (4- (piperidin-1-ylmethyl) anilino) -1-propylmethylene] -6-carbamoyl-2 indolinone: the compound was obtained from the resin obtained according to example P (4) and 4 (piperidin-1-ylmethyl) aniline,

K-value: 0.37 (silica gel, methylene chloride / methanol in the ratio 4: 1), ^C 25 ^Η 30 ^N 4 ^O 2 ^, mass spectrum: t / = 418 (M ⁴ );

(3 9) trifluoroacetate 3 -Ζ- [1- (3-dimethylaminomethylanilino) -1-propylmethylene] -6-carbamoyl-2 indolinone: the compound was obtained from the resin obtained according to Example P (4) and 3d-dimethylaminomethylaniline,

K _g value: 0.42 (silica gel, methylene chloride / methanol in the ratio 4: 1), ^C 22 ^Η 26 ^N 4 ^O 2 ^, mass spectrum: t / = 378 (M ⁴ );

- 37 006080 (40) trifluoroacetate 3 ^ - [1- (4- (No.methyl-No.benzylaminomethyl) anilino) -1-propylmethylene] -6-carbamoyl-2-indolinone: the compound obtained is obtained from obtained according to example P (4) resin and 4 (Ν-methyl-Ν-benzylaminomethyl) aniline,

In _g value: 0.81 (silica gel, methylene chloride / methanol in the ratio 4: 1), ^C '28 ^H 30Y' | ^O 2 · mass spectrum: t / ζ = 454 (M ⁺ );

(41) trifluoroacetate 3 ^ - [1- (4- (No. methylsulfonyl-No. (2-dimethylaminoethyl) amino) anilino) -1-propylmethylene] -6-carbamoyl-2-indolinone: the compound obtained is obtained from obtained according to example P ( 4) resin and 4- (No. methylsulfonyl-No. (2-dimethylaminoethyl) amino) aniline,

The value: 0.59 (silica gel, methylene chloride / methanol 4: 1),

C24H31 ^ O4§, mass spectrum: t / ζ = 486 (M + H ⁺ );

(42) 3 ^ - [1- (4-chloroanilino) -1-propylmethylene] -6-carbamoyl-2-indolinone: the compound is obtained from the resin obtained according to example P (4) and 4-chloroaniline,

In _g value: 0.17 (silica gel, methylene chloride / methanol in the ratio 9: 1), ^C 19 ^Η 18 ^C 1 ^N 3 ^O 2 ^, mass spectrum: t / ζ = 355/357 (M ⁺ );

(43) 3 ^ - [1- (3-chloroanilino) -1-propylmethylene] -6-carbamoyl-2-indolinone: the compound is obtained from the resin obtained according to example P (4) and 3-chloroaniline,

B value: 0.12 (silica gel, methylene chloride / methanol in the ratio 9: 1), mass spectrum: t / ζ = 355/357 (M ⁺ );

(44) 3-Ζ- [1 - (4-methoxycarbonylanilino) -1-propylmethylene] -6-carbamoyl-2-indolinone: the compound is obtained from the resin obtained according to example P (4) and 4-aminobenzoic acid methyl ester,

In _g value: 0.8 (silica gel, methylene chloride / methanol in the ratio 4: 1), mass spectrum: t / ζ = 379 (M ⁺ );

(45) 3 ^ - [1- (4-carboxyanilino) -1-propylmethylene] -6-carbamoyl-2-indolinone: the compound is obtained from the resin obtained according to example P (4) and 4-aminobenzoic acid, mass spectrum: t / ζ = 364 (M-H ⁺ );

(46) 3 ^ - [1- (4-methyl-3-nitroanilino) -1-propylmethylene] -6-carbamoyl-2-indolinone: the compound is obtained from the resin obtained according to example P (4) and 4-methyl-3 -nitroaniline,

In _g value: 0.86 (silica gel, methylene chloride / methanol in the ratio 4: 1), ^C 20 ^Η 20 ^N 4 ^O 4 ^, mass spectrum: t / ζ = 380 (M ⁺ ).

Example 2. Trifluoroacetate 3 ^ - [1- (3- (piperidin-1-ylmethyl) anilino) -1-phenylmethylene] -6-carbamoyl-2-indolinone.

2.0 g of the resin obtained according to Example II is subjected, as in Example 1, to reaction with 2.0 g of 3-aminobenzyl alcohol in 20 ml of dimethylformamide for 22 hours at 70 ° C. After that, the solvent is suction filtered and the resin is washed several times with dimethylformamide and methylene chloride. Then, 200 mg of a wet saturated resin are suspended in 2 ml of methylene chloride and incubated for 2 hours at room temperature with 0.2 ml of methanesulfonic acid chloride and 0.1 ml of triethylamine. Next, the resin is washed several times with methylene chloride, suspended in 2 ml of methylene chloride and mixed with 0.2 ml of piperidine. After 1 h, the resin is washed with methylene chloride and dimethylformamide and then, analogously to example 1, is treated with trifluoroacetic acid.

Yield: 15 mg,

In _g value: 0.30 (silica gel, methylene chloride / methanol in the ratio 4: 1), ^C 28 ^Η 28 ^N 4 ^O 2 ^, mass spectrum: t / = 452 (M ⁺ ).

Analogously to example 2, the following compounds are obtained:

(1) 3 -Ζ- [1 - (3- (diethylaminomethyl) anilino) -1-phenylmethylene] -6-carbamoyl-2-indolinone trifluoroacetate: the compound was obtained from the resin obtained according to example II and diethylamine,

The value: 0.80 (silica gel, methylene chloride / methanol in the ratio 4: 1), ^C 27 ^H 28- ^No . 4 ^O 2.

mass spectrum: t / ζ = 440 (M ⁺ );

(2) 3-Ζ- [1 - (3- (benzylaminomethyl) anilino) -1-phenylmethylene] -6-carbamoyl-2-indolinone trifluoroacetate: the compound was obtained from the resin obtained in Example II and benzylamine,

In _g value: 0.80 (silica gel, methylene chloride / methanol in the ratio 4: 1), ^C 30 ^Η 26 ^N 4 ^O 2 ^, mass spectrum: t / = 474 (M ⁺ );

- 38 006080 (3) trifluoroacetate 3-Ζ- [1 - (3- (#methyl-I-benzylaminomethyl) anilino) -1-phenylmethylene] -6-carbamoyl-2-indolinone: the compound was obtained from the resin obtained according to example II and Ν methylbenzylamine,

K-value: 0.80 (silica gel, methylene chloride / methanol in the ratio 4: 1), ^C 31 ^Η 28 ^N 4 ^O 2 ^, mass spectrum: t / = 488 (M ⁺ );

(4) 3 -Ζ- [1 - (3 - (butylaminomethyl) anilino) -1-phenylmethylene] -6-carbamoyl-2-indolinone trifluoroacetate: the compound was obtained from the resin obtained according to example II and butylamine,

K-value: 0.40 (silica gel, methylene chloride / methanol in the ratio 4: 1), ^C 27 ^H 28 ^ 4 ^O 2, mass spectrum: t / ζ = 440 (M ⁺ );

(5) 3 -Ζ- [1- (3- (aminomethyl) anilino) -1-phenylmethylene] -6-carbamoyl-2-indolinone trifluoroacetate: the compound was obtained from the resin and ammonia obtained according to example II, ^C 23 ^Η 20 ^N 4 ^O 2 ^, mass spectrum: t / ζ = 385 (M + H ⁺ );

(6) 3-Ζ- [1 - (3- (Ν- (3-dimethylaminopropyl) -Y-methylaminomethyl) anilino) -1-phenylmethylene] -6-carbamoyl-2-indolinone trifluoroacetate: the compound obtained from the compound obtained according to example II resin and 1-dimethylamino-3-methylaminopropane,

K-value: 0.67 (silica gel, methylene chloride / methanol in the ratio 4: 1), ^^ 33 ^ ¾ mass spectrum: t / ζ = 484 (M + H ⁺ );

(7) trifluoroacetate 3 ^ - [1- (3- (no. (2-dimethylaminoethyl) -Y-methylaminomethyl) anilino) -1-phenylmethylene] -6-carbamoyl-2-indolinone: the compound was obtained from the resin obtained according to example II and 1-dimethylamino-2-methylaminoethane, ^ {- value: 0.40 (silica gel, methylene chloride / methanol in a 4: 1 ratio), ^C 28 ^Η 31 ^N 5 ^O 2 ^, mass spectrum: t / ζ = 470 (M + H ⁺ ).

Example 3. 3 ^ - [1- (4- (piperidin-1-ylmethyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone.

1.5 g of 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-ethoxycarbonyl-2-indolinone and 1.1 g of 4- (piperidin1-ylmethyl) aniline are dissolved in 15 ml of dimethylformamide and stirred for 45 min at 100 ° C. After cooling, 5.0 ml of piperidine is added and the mixture is stirred for 3 hours at room temperature. After that, the solvent is distilled off and the residue is purified on a column with alumina (activity 2-3) using methylene chloride / ethanol (100: 3) as a solvent.

Output: 1.1 g (58% of theory), ^ {- value: 0.5 (aluminum oxide, methylene chloride / ethanol in a ratio of 100: 3), ^C 30 ^Η 31 ^N 3 ^O 3 ^, mass spectrum: t / ζ = 481 [M ⁺ ].

Analogously to example 3, the following compounds are obtained:

(1) 3 ^ - [1- (4-bromoanilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone: this compound is obtained from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6- ethoxycarbonyl-2-indolinone and 4-bromoaniline,

K-value: 0.4 (silica gel, toluene / ethyl acetate in the ratio 5: 1),

C24H1 ₉ VG ^ Oe, mass spectrum: t / ζ = 462/464 | M '];

(2) 3 -Ζ - [1 - (3- (dimethylaminomethyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone: the specified compound is obtained from 1-acetyl-3- (1-ethoxy-1-phenylmethylene ) -6-ethoxycarbonyl-2-indolinone and 3- (dimethylaminomethyl) aniline,

K-value: 0.5 (aluminum oxide, methylene chloride / ethanol in a ratio of 30: 1), ^C 27 ^Η 27 ^N 3 ^O 3 ^, mass spectrum (EM): t / ζ = 442 [M + H ⁺ ];

(3) 3 ^ - [1- (4- (dimethylaminomethyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone: this compound is obtained from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-ethoxycarbonyl-2-indolinone and 4- (dimethylaminomethyl) aniline,

K-value: 0.7 (alumina, ethyl acetate / ethanol in a ratio of 20: 1),

C27H27 ^ O ₃ , mass spectrum (EM): t / ζ = 442 [M + H ⁺ ];

(4) 3 ^ - [1- (4 - [(2,6-dimethylpiperidin-1-yl) methyl] anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2indolinone: said compound is obtained from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6 ethoxycarbonyl-2-indolinone and 4 - [(2,6-dimethylpiperidin-1-yl) methyl] aniline,

K-value: 0.6 (silica gel, methylene chloride / ethanol 5: 1 ratio),

- 39 006080 ^С 32 ^H 35 ^N 3 ^О 3 ^, mass spectrum: t / = 509 [M];

(5) 3 -Ζ- [1- (4- (2-dimethylaminoethyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone: this compound is obtained from 1-acetyl-3- (1-ethoxy-1 -phenylmethylene) -6-ethoxycarbonyl-2-indolinone and 4- (2-dimethylaminoethyl) aniline,

K-value: 0.2 (silica gel, methylene chloride / ethanol in the ratio 5: 1),

C28H2 ₉ No. Oe, mass spectrum: t / ζ = 455 | M '];

(6) 3 -Ζ- [1 - (4- (No. (2-dimethylaminoethyl) -N. acetylamino) cap)) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone: the compound obtained is obtained from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-ethoxycarbonyl-2-indolinone and 4- (No. (2-dimethylaminoethyl) -Noacetylamino) aniline,

K-value: 0.4 (aluminum oxide, methylene chloride / ethanol in a ratio of 20: 1), ^C 30 ^H 32 ^N 4 ^O 4 ^, mass spectrum: t / ζ = 512 [M ⁴ ];

(7) 3 ^ - [1- (4-tert-Butyloxycarbonylanilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone: this compound is obtained from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) - 6-ethoxycarbonyl-2-indolinone and 4-tert-butyloxycarbonylaniline,

K-value: 0.4 (aluminum oxide, methylene chloride / ethanol in a ratio of 40: 1),

C2 ₉ H28 ^ O5, mass spectrum: t / ζ = 484 [M];

(8) 3 ^ - [1- (4- (No. (3-dimethylaminopropyl) -Noacetylamino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone: said compound is obtained from 1-acetyl-3- ( 1-ethoxy-1-phenylmethylene) -6 ethoxycarbonyl-2-indolinone and 4- (Ν- (3-dimethylaminopropyl) -N acetylamino) aniline,

K-value: 0.2 (aluminum oxide, methylene chloride / ethanol in the ratio of 40: 1), mass spectrum: t / ζ = 526 [M ⁴ ];

(9) 3 -Ζ - [1 - (4- (No. (2-dimethylaminoethyl) -Nomethylsulfonylamino) anilino) -1-phenylmethylene] -6ethoxycarbonyl-2-indolinone: the compound is obtained from 1-acetyl-3- (1 -ethoxy-1phenylmethylene) -6-ethoxycarbonyl-2-indolinone and No. (2-dimethylaminoethyl) - мет methylsulfonyl-pphenylenediamine,

K-value: 0.3 (aluminum oxide, methylene chloride / ethanol in a ratio of 40: 1),

C2 ₉ He2№O58, mass spectrum: t / ζ = 548 [M ⁴ ];

(10) 3 -Ζ- [1 - (4- (4-methylpiperazin-1-yl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone: said compound is obtained from 1-acetyl-3- (1 ethoxy-1-phenylmethylene) -6-ethoxycarbonyl-2-indolinone and 4- (4-methylpiperazin-1-yl) aniline,

K-value: 0.3 (alumina, ethyl acetate), ^C 29 ^H 30 ^N 4 ^O 3 ^, mass spectrum (Е8Ц: t / = 483 [M + H ⁴ ];

(11) 3 -Ζ- [1- (4- (C- (2-dimethylaminoethyl) -Nomethylamino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone: said compound is obtained from 1-acetyl-3 - (1-ethoxy-1-phenylmethylene) -6 ethoxycarbonyl-2-indolinone and 4- (No. (2-dimethylaminoethyl) -N.methylamino) aniline,

Purpose: 0.5 (aluminum oxide, methylene chloride / ethanol in a ratio of 20: 1),

С2 ₉ Н32№Оэ, mass spectrum (Е8Ц: t / ζ = 485 [M + H ⁴ ];

(12) 3 -Ζ- [1- (4- (Ν- (3-dimethylaminopropyl) -Nmethylamino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone: the compound obtained is derived from 1-acetyl-3 - (1-ethoxy-1-phenylmethylene) -6 ethoxycarbonyl-2-indolinone and 4- (Ν- (3-dimethylaminopropyl) -№ methylamino) aniline,

K _g value: 0.5 (aluminum oxide, ethyl acetate), ^C 30 ^H 34 ^N 4 ^O 3 ^, mass spectrum (Е8Ц: t / ζ = 499 [М4Н ⁴ ];

(13) 3 ^ - [1- (4- (C-methylacetylamino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone: this compound is obtained from 1-acetyl-3- (1-ethoxy-1- phenylmethylene) -6-ethoxycarbonyl-2-indolinone and 4-amino-No. methyl acetanilide,

Kg value: 0.3 (silica gel, methylene chloride / ethanol in the ratio 15: 1), ^С 2- ^Н 25 ^N 3 ^О 4 ^, mass spectrum: t / ζ = 455 [М ⁴ ];

(14) 3 -Ζ- [1- (4- (C-methylmethylsulfonylamino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2indolinone: the compound is obtained from 1-acetyl-3- (1-ethoxy-1-phenylmethylene ) -6-ethoxycarbonyl-2-indolinone and No. (4-aminophenyl) -Mnomethanesulfonamide,

K _g value: 0.8 (alumina, ethyl acetate), ^C 26 ^H 25 ^N 3 ^O 5 ^8,

- 40 006080 mass spectrum: t / = 491 [M ⁺ ];

(15) 3 -Ζ- [1- (4- (Ν- (3-dimethylaminopropyl) -Nomethylsulfonylamino) anilino) -1-phenylmethylene] -6 ethoxycarbonyl-2-indolinone: the compound is obtained from 1-acetyl-3- ( 1-ethoxy-1-phenylmethylene) -6-ethoxycarbonyl-2-indolinone and No. (3-dimethylaminopropyl) -No methylsulfonyl-p-phenylenediamine,

K ~ value: 0.6 (silica gel, methylene chloride / ethanol / ammonia in a ratio of 5: 2: 0.01),

Szoyz4N4Ο58, mass spectrum (E8C: t / ζ = 563 [Μ + Η];

(16) 3 -Ζ- [1 - (4- (No. dimethylaminocarbonylmethyl-No.methylsulfonylamino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone: this compound is obtained from 1-acetyl-3- (1-ethoxy -1-phenylmethylene) -6-ethoxycarbonyl-2-indolinone and 4- (No. dimethylaminocarbonylmethyl-No. methylsulfonyl) amino) aniline,

K-value: 0.6 (silica gel, methylene chloride / ethanol in the ratio 10: 1), ^С 29 ^Η 30 ^N 4 ^Ο 6 ^ ^, mass spectrum (Е8Ц: t / ζ = 561 [M-H ⁺ ];

(17) 3-Ζ- [1- (4- (imidazol-4-yl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone: this compound is obtained from 1-acetyl-3- (1-ethoxy -1-phenylmethylene) -6-ethoxycarbonyl-2-indolinone and 4 (imidazol-4-yl) aniline,

K-value: 0.5 (silica gel, methylene chloride / ethanol / ammonia in a ratio of 10: 1: 0.01),

C27SH2 ^ O3, mass spectrum: t / ζ = 450 | M '];

(18) 3 -Ζ- [1- (4- (tetrazol-5-yl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone: this compound is obtained from 1-acetyl-3- (1-ethoxy -1-phenylmethylene) -6-ethoxycarbonyl-2-indolinone and 4 (tetrazol-5-yl) aniline,

K-value: 0.5 (silica gel, methylene chloride / ethanol in the ratio 5: 1), ^C 25 ^Η 20 ^N 6 ^Ο 3 ^, mass spectrum (Е8Ц: t / ζ = 451 [M-H ⁺ ]);

(19) 3 -Ζ- [1 - (4- (No.Benzyl-No.methylaminomethyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2indolinone: the compound is obtained from 1-acetyl-3- (1-ethoxy-1 -phenylmethylene) -6-ethoxycarbonyl-2-indolinone and 4- (No.benzyl-No.methylaminomethyl) aniline,

K-value: 0.4 (silica gel, methylene chloride / ethanol in a ratio of 10: 1),

C33K1 ^ O3, mass spectrum (E8C: t / ζ = 516 [M – H ⁺ ];

(20) 3 -Ζ - [1 - (4- (P- (2-dimethylaminoethyl) -Npropionylamino) aniline) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone: this compound is obtained from 1-acetyl-3 - (1-ethoxy-1-phenylmethylene) -6 ethoxycarbonyl-2-indolinone and 4- [No.

K-value: 0.2 (silica gel, methylene chloride / ethanol in the ratio 5: 1), mass spectrum (E8C: t / ζ = 525 [M – H];

(21) 3 -Ζ - [1- (4- (pyrrolidin-1-ylmethyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone: this compound is obtained from 1-acetyl-3- (1-ethoxy -1-phenylmethylene) -6-ethoxycarbonyl-2-indolinone and 4- (pyrrolidin-1-ylmethyl) aniline,

K-value: 0.1 (silica gel, methylene chloride / ethanol 5: 1 ratio),

C29H29 ^ O3, mass spectrum (E8C: t / ζ = 466 [M – H ^- ];

(22) 3 ^ - [1- (4- (P-methyl-N-phenethylaminomethyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2indolinone: the compound is obtained from 1-acetyl-3- (1-ethoxy-1 -phenylmethylene) -6-ethoxycarbonyl-2-indolinone and 4- (No.phenethyl-No.methylaminomethyl) aniline,

K-value: 0.4 (silica gel, methylene chloride / ethanol in the ratio 10: 1), ^ ₄ Ν ₃₃ Ν ₃ Ο ₃ , mass spectrum (E8Ts: t / ζ = 530 [M-H ^- ];

(23) 3 ^ - [1- (4- (No. dimethylaminomethylcarbonyl-No.methylamino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone: this compound is obtained from 1-acetyl-3- (1-ethoxy- 1-phenylmethylene) -6 ethoxycarbonyl-2-indolinone and dimethylaminomethylcarbonyl-methyl-p-phenylenediamine,

K-value: 0.1 (silica gel, methylene chloride / ethanol in the ratio 10: 1), ^С 29 ^Η 30 ^N 4 ^Ο 4 ^, mass spectrum (Е8Ц: t / ζ = 497 [M-H ^- ];

(24) 3 ^ - [1- (4- (No. (2-dimethylaminoethyl) -Noethylsulfonylamino) anilino) -1-phenylmethylene] -6ethoxycarbonyl-2-indolinone: this compound is obtained from 1-acetyl-3- (1- ethoxy-1phenylmethylene) -6-ethoxycarbonyl-2-indolinone and No. (2-dimethylaminoethyl) -Noethylsulfonyl-pphenylenediamine,

K-value: 0.6 (silica gel, methylene chloride / ethanol 5: 1 ratio),

- 41 006080 ^С 30Ηз4N4 ^О 58 ^, mass spectrum (Ε8Ι): t / ζ = 561 [M – H ⁺ ];

(25) 3 -Ζ- [1 - (4- (L-tert-butoxycarbonyl-M-ethylaminomethyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone: said compound is obtained from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6 ethoxycarbonyl-2-indolinone and 4- (M-tert-butoxycarbonyl-M-ethylaminomethyl) aniline,

I _g value: 0.5 (silica gel, methylene chloride / methanol in a ratio of 10: 1),

C32H35Y3O5, mass spectrum (Ε8Ι): t / ζ = 540 [M – H ^- ];

(26) 3 -Ζ- [1- (4- (piperidin-1-methylmethyl) anilino) -1-ethylmethylene] -6-ethoxycarbonyl-2-indolinone: this compound is obtained from 1-acetyl-3- (1-ethoxy -1-ethylmethylene) -6-ethoxycarbonyl-2-indolinone and 4- (piperidin-1-ylmethyl) aniline,

I _g value: 0.9 (silica gel, methylene chloride / ethanol 5: 1 ratio),

COUNT ;, mass spectrum (Ε8Ι): t / ζ = 432 [M – H ^- ];

(27) 3 ^ - [1- (4- (K- (2-dimethylaminoethyl) -H-methylsulfonylamino) anilino) -1-ethylmethylene] -6-ethoxycarbonyl-2-indolinone: the compound is obtained from 1-acetyl-3 - (1-ethoxy-1-ethylmethylene) -6 ethoxycarbonyl-2-indolinone and N- (2-dimethylaminoethyl) -N-methylsulfonyl-p-phenylenediamine,

I ^ -value: 0,3 (silica gel, methylene chloride / ethanol in the ratio 5: 1),

C25B32X4O58, mass spectrum (Ε8Ι): t / ζ = 499 [M – H ^- ];

(28) 3 ^ - [1- (4- (dimethylaminomethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone: the compound is obtained from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-methoxycarbonyl-2-indolinone and 4- (dimethylaminomethyl) aniline,

I _g value: 0.6 (silica gel, methylene chloride / methanol in the ratio 5: 1), ^C 26 ^Η 25 ^N 3 ^O 3 ^, mass spectrum (Ε8 Ι): t / ζ = 428 [M + H ⁺ ];

(29) 3 ^ - [1- (4 - [(2,6-dimethylpiperidin-1-yl) methyl] anilino) -1-phenylmethylene] -6-methoxycarbonyl2-indolinone: said compound is obtained from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-methoxycarbonyl-2-indolinone and 4 - [(2,6-dimethylpiperidin-1-yl) methyl] aniline,

Ya value: 0.5 (reversed phase YAR 8, methanol / 5% solution of sodium chloride in the ratio 4: 1),

C31I33M3O3, mass spectrum (Ε8Ι): t / = 496 [M + H ⁺ ];

(30) 3 ^ - [1- (4- (L- (2-dimethylaminoethyl) -H-methylsulfonylamino) anilino) -1-phenylmethylene] -6methoxycarbonyl-2-indolinone: the compound is obtained from 1-acetyl-3- ( 1-ethoxy-1-phenylmethylene) -6-methoxycarbonyl-2-indolinone and N- (2-dimethylaminoethyl) -N-methylsulfonyl-p-phenylenediamine,

I _g value: 0.6 (silica gel, methylene chloride / methanol in the ratio 5: 1), ^C 28 ^Η 30 ^N 4 ^O 5 ^ ^, mass spectrum (Ε 8 Ι): t / ζ = 533 [M – H ⁺ ];

(31) 3 -Ζ- [1- (4- (Ν- (3-dimethylaminopropyl) -Y-methylsulfonylamino) anilino) -1-phenylmethylene] -6methoxycarbonyl-2-indolinone: the compound is obtained from 1-acetyl-3- (1-ethoxy-1phenylmethylene) -6-methoxycarbonyl-2-indolinone and Ν- (3-dimethylaminopropyl) -Y-methylsulfonyl-pphenylenediamine,

Ratio: 0.5 (aluminum oxide, methylene chloride / methanol in a ratio of 30: 1),

C29I32CHO58, mass spectrum (Ε8Ι): t / ζ = 547 [M – H ^- ];

(32) 3 ^ - [1- (4- (K-dimethylaminocarbonylmethyl-N-methylsulfonylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone: the compound is obtained from 1-acetyl-3- (1- ethoxy-1phenylmethylene) -6-methoxycarbonyl-2-indolinone and 4-U-dimethylaminocarbonylmethyl-N-methylsulfonyl) amino) aniline,

Ratio: 0.5 (alumina, methylene chloride / methanol 20: 1),

C28I28CHO68, mass spectrum (Ε8Ι): t / ζ = 547 [Ν-H ^- ];

(33) 3 -Ζ- [1- (4-U-acetyl-H-dimethylaminocarbonylmethylamino) anilino) -1-phenylmethylene] -6methoxycarbonyl-2-indolinone: the title compound is obtained from 1-acetyl-3- (1-ethoxy- 1-phenylmethylene) -6-methoxycarbonyl-2-indolinone and 4-U-acetyl-I-dimethylaminocarbonylmethyl) amino) aniline,

I _g value: 0.6 (silica gel, methylene chloride / methanol in the ratio 10: 1), ^C 29I28AO5, mass spectrum (Ε8Ι): t / ζ = 511 [Ν-Н ^- ];

- 42 006080 (34) 3-2- [1- (4- (№ dimethylaminocarbonylmethylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone: the specified connection is obtained from 1-acetyl-3- (1-ethoxy -1-phenylmethylene) -6methoxycarbonyl-2-indolinone and 4- (dimethylaminocarbonylmethyl) amino) aniline,

B value: 0.6 (aluminum oxide, methylene chloride / methanol 30: 1), 27 ^C 26 ^N 4 ^Η ^Ο ^4, MS (EM): m / ζ = 469 [Ν-H ^-];

(35) 3 -Ζ- [1- (4- (Ν- (3-dimethylaminopropyl) -N acetylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone: the compound obtained is obtained from 1-acetyl-3 - (1-ethoxy-1-phenylmethylene) -6methoxycarbonyl-2-indolinone and N- (3-dimethylamino-propyl) -N. acetyl-p-phenylenediamine,

B value: 0.5 (aluminum oxide, methylene chloride / methanol 20: 1), ^C 30 32 ^N 4 ^Η ^Ο ^4, MS (EM): m / ζ = 511 [M-H ^-];

(36) 3 -Ζ- [1 - (4- (No.methylaminocarbonylmethyl-No.methylsulfonylamino) anilino) -1-phenylmethylene] 6-methoxycarbonyl-2-indolinone: this compound is obtained from 1-acetyl-3- (1-ethoxy- 1phenylmethylene) -6-methoxycarbonyl-2-indolinone and No. methylaminocarbonylmethyl-No. methylsulfonyl-phenylenediamine,

B-value: 0.5 (silica gel, methylene chloride / methanol in a ratio of 10: 1),

C27H26 ^ O6§, mass spectrum (EM): t / ζ = 533 [M – H ^- ];

(37) 3 -Ζ- [1 - (4 - ((imidazolidin-2,4-dione-5-ylidene) methyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone: said compound is obtained from 1 -acetyl-3- (1-ethoxy-1-phenylmethylene) -6methoxycarbonyl-2-indolinone and 4 - ((imidazolidin-2,4-dione-5-ylidene) methyl) aniline,

B-value: 0.4 (silica gel, methylene chloride / methanol in the ratio 10: 1), ^С 2 ₇ Н20 ^ О5, mass spectrum (ЕМ): t / ζ = 479 [М-Н ^- ];

(3 8) 3 -Ζ- [1 - (4- (No. ((2-dimethylaminoethyl) carbonyl) -Nomethylamino) anilino) -1-phenylmethylene] -6 methoxycarbonyl-2-indolinone: this compound is obtained from 1-acetyl- 3- (1-ethoxy-1phenylmethylene) -6-methoxycarbonyl-2-indolinone and No. ((2-dimethylaminoethyl) carbonyl) -№ methyl-pphenylenediamine,

B value: 0.5 (aluminum oxide, methylene chloride / methanol 20: 1), 29 ^C 30 ^N 4 ^Η ^Ο ^4, MS (EM): m / ζ = 497 [M-H ^-];

(3 9) 3 -Ζ- [1- (4- (No. tert-butoxycarbonylaminomethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone: the compound is obtained from 1-acetyl-3- (1-ethoxy -1-phenylmethylene) -6methoxycarbonyl-2-indolinone and 4- (No. tert-butoxycarbonylaminomethyl) aniline,

B-value: 0.3 (aluminum oxide, methylene chloride / methanol in a ratio of 20: 1), ^C 29 ^Η 29 ^N 3 ^Ο 5 ^, mass spectrum (EM): t / ζ = 498 [M – H ^- ];

(40) 3 -Ζ- [1- (4- (2-oxopyrrolidin-1-ylmethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2indolinone: the compound is obtained from 1-acetyl-3- (1-ethoxy -1-phenylmethylene) -6-methoxycarbonyl-2-indolinone and 4- (2-oxopyrrolidin-1-ylmethyl) aniline,

B-value: 0.3 (silica gel, methylene chloride / methanol in a ratio of 20: 1), ^C 28 ^H 25 ^N 3θ4 ^, mass spectrum (EM): t / ζ = 466 [M – H];

(41) 3 ^ - [1- (4- (No. aminocarbonylmethyl-No.methylsulfonylamino) anilino) -1-phenylmethylene] -6methoxycarbonyl-2-indolinone: this compound is obtained from 1-acetyl-3- (1-ethoxy-1- phenylmethylene) -6-methoxycarbonyl-2-indolinone and No. aminocarbonylmethyl-No.methylsulfonyl-p-phenylenediamine,

B value: 0.7 (silica gel, methylene chloride / methanol = 5: 1), ^C 26 24 ^N 4 ^Η ^Ο 6 ^{^,} MS (EM): m / ζ = 519 [M-H ^-];

(42) 3 -Ζ - [1- (4- (thiomorpholin-4-ylmethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone: this compound is obtained from 1-acetyl-3- (1-ethoxy -1-phenylmethylene) -6-methoxycarbonyl-2 indolinone and 4- (thiomorpholin-4-ylmethyl) aniline,

B-value: 0.4 (silica gel, methylene chloride / methanol in a ratio of 15: 1),

C28H2 ₇ ^ OeM mass spectrum (EM): t / ζ = 484 [M – H ^- ];

(43) 3 -Ζ - [1 - (4- (1,1-dioxothiomorpholin-4-ylmethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl2-indolinone: the title compound is obtained from 1-acetyl-3- (1 ethoxy-1-phenylmethylene) -6 methoxycarbonyl-2-indolinone and 4- (1,1-dioxothiomorpholin-4-ylmethyl) aniline,

B value: 0.5 (silica gel, methylene chloride / methanol = 10: 1), ^C 28 ^N 3 27 ^Η ^Ο ^ ^5,

- 43 006080 mass spectrum (Е8Ц: t / ζ = 516 [M – H ^- ];

(44) 3 -Ζ- [1 - (4- (#cyanomethyl-No.methylsulfonylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone: the compound is obtained from 1-acetyl-3- (1-ethoxy -1-phenylmethylene) -6methoxycarbonyl-2-indolinone and No. cyanomethyl-No.methylsulfonyl-p-phenylenediamine,

K-value: 0.6 (silica gel, methylene chloride / methanol in the ratio 10: 1), ^С 26 ^Н 22У '| ^About 58.

mass spectrum (E8C: t / ζ = 501 [M – H];

(45) 3 -Ζ- [1- (4- (No. tert-butoxycarbonylethylaminomethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone: this compound is obtained from 1-acetyl-3- (1-ethoxy- 1-phenylmethylene) -6methoxycarbonyl-2-indolinone and 4- (No. ethyl-no. T-butoxycarbonylaminomethyl) aniline,

K-value: 0.6 (silica gel, methylene chloride / methanol in a ratio of 10: 1),

SeShee ^ On, mass spectrum (E8C: t / / = 526 [M – H];

(46) 3 -Ζ- [1 - (4- (No.Benzyl-No.methylaminomethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2indolinonon: the compound is obtained from 1-acetyl-3- (1-ethoxy-1 -phenylmethylene) -6-methoxycarbonyl-2-indolinone and 4- (No.benzyl-No.methylaminomethyl) aniline,

K-value: 0.5 (silica gel, methylene chloride / methanol in a ratio of 10: 1),

Ce2H29 ^ Oe, mass spectrum (E8C: t / ζ = 502 [M – H ^- ];

(47) 3 ^ - [1- (4- (1-oxothiomorpholin-4-ylmethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2indolinone: this compound is obtained from 1-acetyl-3- (1-ethoxy- 1-phenylmethylene) -6-methoxycarbonyl-2-indolinone and 4- (1-oxiomorpholin-4-ylmethyl) aniline,

K-value: 0.7 (silica gel, methylene chloride / methanol in the ratio 10: 1), ^С 28Н27 ^ О4§, mass spectrum (Е8Ц: t / ζ = 500 [М-Н ^- ];

(48) 3 ^ - [1- (4- (2- (imidazol-4-yl) ethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone: this compound is obtained from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-methoxycarbonyl-2-indolinone and 4- (2- (imidazol-4-yl) ethyl) aniline,

K-value: 0.4 (silica gel, methylene chloride / methanol 5: 1 ratio),

C28H24 ^ O ₃ , mass spectrum (E8C: t / ζ = 463 [M – H ^- ];

(49) 3 ^ - [1- (4- (morpholin-4-ylmethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone: this compound is obtained from 1-acetyl-3- (1-ethoxy- 1-phenylmethylene) -6-methoxycarbonyl-2-indolinone and 4- (morpholin-4-ylmethyl) aniline,

K-value: 0.5 (silica gel, methylene chloride / methanol in a ratio of 10: 1), ^C 28 ^H 27 ^N 3 ^O 4 ^, mass spectrum (E 8 C: t / ζ = 468 [M – H ^- ];

(50) 3 -Ζ- [1 - (4 - ((4-methylpiperazin-1-yl) methyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2indolinone: said compound is obtained from 1-acetyl-3- ( 1-ethoxy-1-phenylmethylene) -6-methoxycarbonyl-2-indolinone and 4 - ((4-methylpiperazin-1-yl) methyl) aniline,

K-value: 0.4 (silica gel, methylene chloride / methanol 5: 1 ratio),

C2 ₉ H30 ^ Oe, mass spectrum (E8C: t / ζ = 481 [M – H ^- ];

(51) 3 -Ζ- [1 - (4 - ((2- (No.benzyl-No.methylamino) ethyl) -Nomethylsulfonylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone: the compound is obtained from 1-acetyl-3- (1-ethoxy-1phenylmethylene) -6-methoxycarbonyl-2-indolinone and 4- (No. (2- (No.benzyl-No.methylamino) ethyl) -Nomethylsulfonylamino) aniline,

K-value: 0.7 (silica gel, methylene chloride / methanol in a ratio of 10: 1),

C ₃₄ H ₃₄ ^ O ₅ 8, mass spectrum (E8C: t / ζ = 609 [M – H ^- ];

(52) 3 ^ - [1- (4-cyclohexylaminoanilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone: this compound is obtained from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6- methoxycarbonyl-2-indolinone and Ν-cyclohexyl-p-phenylenediamine,

K-value: 0.8 (silica gel, methylene chloride / methanol in a ratio of 10: 1),

C2 ₉ H28 ^ Oz, mass spectrum (E8Ts: t / ζ = 451 [M-H ^- ];

(53) 3-Ζ- [1- (4- (pyridin-4-ylmethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone: this compound is obtained from 1-acetyl-3- (1-ethoxy -1-phenylmethylene) -6-methoxycarbonyl-2-indolinone and 4- (pyridin-4-ylmethyl) aniline,

K-value: 0.6 (silica gel, methylene chloride / methanol / ammonia in the ratio 5: 1: 0.01), ^C 29 ^H 23 ^N 3 ^O 3 ^, mass spectrum (E8C: t / ζ = 460 [M-H ^- ];

- 44 006080 (54) 3 -Ζ- [1 - (4- (imidazol-1-methylmethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone: this compound is obtained from 1-acetyl-3- ( 1-ethoxy-1-phenylmethylene) -6-methoxycarbonyl-2-indolinone and 4- (imidazol-1-ylmethyl) aniline,

K _g value: 0.4 (silica gel, methylene chloride / methanol / ammonia in the ratio 10: 1: 0.01), ^C 27 ^Η 22 ^N 4 ^O 3 ^, mass spectrum (EI): t / ζ = 449 [M- H ^- ];

(55) 3-Ζ- [1- (4- (imidazol-1-methylmethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone: the compound is obtained from 1-acetyl-3- (1-ethoxy -1-phenylmethylene) -6-methoxycarbonyl-2-indolinone and 4- (imidazol-1-ylmethyl) aniline,

K-value: 0.4 (silica gel, methylene chloride / methanol / ammonia in a ratio of 10: 1: 0.01),

C27H22KO3, mass spectrum (UI): t / ζ = 449 [M – H ^- ];

(56) 3 -Ζ- [1 - (No. methylpiperidin-4-ylamino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone: the specified compound is obtained from 1-acetyl-3- (1-ethoxy-1-phenylmethylene ) -6-methoxycarbonyl-2-indolinone and 4-amino-1-methylpiperidine,

K _g value: 0.3 (silica gel, methylene chloride / methanol in the ratio 5: 1), ^C 23 ^Η 25 ^N 3 ^O 3 ^, mass spectrum (UI): t / ζ = 390 [M – H ^- ];

(57) 3 ^ - [1- (4- (imidazol-4-ylmethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone: this compound is obtained from 1-acetyl-3- (1-ethoxy- 1-phenylmethylene) -6-methoxycarbonyl-2-indolinone and 4- (imidazol-4-ylmethyl) aniline,

K-value: 0.2 (silica gel, methylene chloride / methanol in the ratio 5: 1),

C27H22KO3, mass spectrum (UI): t / ζ = 449 [M – H ^- ];

(58) 3 -Ζ- [1 - (4 - ((4-hydroxypiperidin-1-yl) methyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2indolinone: said compound is obtained from 1-acetyl-3- ( 1-ethoxy-1-phenylmethylene) -6-methoxycarbonyl-2-indolinone and 4 - ((4-hydroxypiperidin-1-yl) methyl) aniline,

K _g value: 0.1 (silica gel, methylene chloride / methanol in a ratio of 10: 1), ^C 29 ^H 29 ^N 3 ^O 3 ^, mass spectrum (UI): t / ζ = 482 [M – H ^- ];

(59) 3 -Ζ- [1 - (4 - ((4-methoxypiperidin-1-yl) methyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2indolinone: said compound is obtained from 1-acetyl-3- ( 1-ethoxy-1-phenylmethylene) -6 methoxycarbonyl-2-indolinone and 4 - (((4-methoxypiperidin-1-yl) methyl) aniline,

K-value: 0.4 (silica gel, methylene chloride / methanol in a ratio of 10: 1), mass spectrum (UI): t / ζ = 496 [M – H ^- ];

(60) 3 ^ - [1- (4-benzylanilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone: this compound is obtained from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6- methoxycarbonyl-2-indolinone and 4benzylaniline,

To _g value: 0.6 (silica gel, methylene chloride / methanol in a ratio of 10: 1),

C30H24KO3,

I: 224 ° C;

(61) 3 -Ζ- [1- (4- (H- (3-trifluoroacetylaminopropyl) -Cmethylsulfonylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone: this compound is obtained from 1-acetyl-3- (1-ethoxy-1phenylmethylene) -6-methoxycarbonyl-2-indolinone and N- (3-trifluoroacetylaminopropyl) -Cmethylsulfonyl-p-phenylenediamine,

_Kg value: 0.5 (aluminum oxide, methylene chloride / methanol in a ratio of 20: 1), ^С 29Н27Е3КО6§, mass spectrum (ЕИ): t / ζ = 615 [М-Н];

(62) 3 -Ζ- [1 - (4-tert-butoxycarbonylmethylanilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone: this compound is obtained from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-ethoxycarbonyl-2 indolinone and 4-aminophenylacetic acid t-butyl ester,

K-value: 0.5 (aluminum oxide, ethyl acetate),

C30H30KO5, mass spectrum (UI): t / ζ = 497 [M – H ^- ];

(63) 3 -Ζ- [1 - (4-tert-butoxycarbonylanilino) -1-ethylmethylene] -6-ethoxycarbonyl-2-indolinone: said compound is obtained from 1-acetyl-3- (1-ethoxy-1-ethylmethylene) -6-ethoxycarbonyl-2-indolinone and 4-tert-butoxycarbonylaniline,

K _g value: 0.4 (aluminum oxide, methylene chloride / ethanol in a ratio of 20: 1), ^C 25 ^Η 28 ^N 2 ^O 5 ^, mass spectrum (Е8!): T / ζ = 435 [M – H ^- ];

- 45 006080 (64) 3-Ζ- [1 - (4- (4-tert-butoxycarbonylpiperazin-1-ylmethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone: said compound obtained from 1-acetyl -3- (1-ethoxy-1-phenylmethylene) -6methoxycarbonyl-2-indolinone and 4- (4-tert-butoxycarbonylpiperazin-1-methylmethyl) aniline,

K-value: 0.5 (silica gel, methylene chloride / methanol in the ratio 10: 1), ^C 33 ^H 36 ^N 4 ^O 5 ^, mass spectrum (E 8 C: t / ζ = 567 [M – H ^- ];

(65) 3 -Ζ- [1- (4- (1-methylimidazol-2-yl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone: this compound is obtained from 1-acetyl-3- (1 ethoxy-1-phenylmethylene) -6-methoxycarbonyl-2-indolinone and 4- (1-methylimidazol-2-yl) aniline,

K-value: 0.6 (silica gel, methylene chloride / methanol 5: 1),

C27H22CHO3, mass spectrum (E8Ц t / ζ = 449 [M – H ^- ];

(66) 3-Ζ- [1- (4-Shch- (2-dimethylaminoethyl) -Nomethylsulfonylamino) -3-nitroanilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone: the compound obtained is obtained from 1-acetyl -3- (1-ethoxy-1phenylmethylene) -6-methoxycarbonyl-2-indolinone and 6-Shch- (2-dimethylaminoethyl) -Nomethylsulfonylamino) -3-aminonitrobenzene,

K-value: 0.6 (silica gel, methylene chloride / methanol 5: 1),

C28H29 ^ O7§, mass spectrum (E8C: t / ζ = 578 [M – H ^- ];

(67) 3-Ζ- [1 - (4-Shch- (2-dimethylaminoethyl) -Nomethylsulfonylamino) -3-amino-anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone: the said compound is obtained from 1-acetyl -3- (1-ethoxy-1phenylmethylene) -6-methoxycarbonyl-2-indolinone and 4-Shch- (2-dimethylaminoethyl) -Nomethylsulfonylamino) -3 -aminoaniline,

K-value: 0.5 (aluminum oxide, methylene chloride / methanol in a ratio of 20: 1), ^C 28 ^Η 31 ^N 5 ^O 58 ^, mass spectrum (E8C: t / ζ = 548 [M – H];

(68) 3-Ζ- [1 - (4 - ((3 - (C-benzyl-Nometilamino) propyl) -Nomethylsulfonylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone: the said compound is obtained from 1-acetyl-3- (1-ethoxy-1phenylmethylene) -6-methoxycarbonyl-2-indolinone and 4-Shch- (3-Sh-benzyl-No.methylamino) propyl) -№methylsulfonylamino) aniline,

K-value: 0.6 (silica gel, methylene chloride / methanol in a ratio of 10: 1),

C35H36CHO5§, mass spectrum (E8C: t / ζ = 623 [M – H ^- ];

(69) 3-Ζ- [1 - (4-Shch- (2-dimethylaminoethyl) -Nomethylsulfonylamino) -3-chloroanilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone: the specified compound is obtained from 1-acetyl -3- (1-ethoxy-1-phenylmethylene) -6-methoxycarbonyl-2-indolinone and 4- (No. (2-dimethylaminoethyl) -№ methylsulfonylamino) -3 chloraniline,

K-value: 0.5 (silica gel, methylene chloride / methanol in a ratio of 10: 1), mass spectrum (E8C t / ζ = 567/569 [M – H ^- ];

(70) 3 ^ - [1- (4-U-dimethylaminomethylcarbonyl-No.methylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone: this compound is obtained from 1-acetyl-3- (1-ethoxy- 1-phenylmethylene) -6methoxycarbonyl-2-indolinone and dimethylaminomethylcarbonyl-methyl-p-phenylenediamine,

K-value: 0.5 (silica gel, methylene chloride / methanol in the ratio 9: 1), ^С 28 ^Η 28 ^N 4 ^О 4 ^, mass spectrum (Е8Ц: t / ζ = 483 [М-Н ^- ];

(71) 3 -Ζ- [1 - (4-Shch- (2-dimethylaminoethyl) -Noacetylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone: the compound is obtained from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6methoxycarbonyl-2-indolinone and 4-Shch- (2-dimethylaminoethyl) -Noacetylamino) aniline,

K-value: 0.5 (silica gel, methylene chloride / methanol in the ratio 9: 1), ^С 29 ^Η 30 ^N 4 ^О 4 ^, mass spectrum (Е8Ц: t / ζ = 497 [М-Н ^- ];

(72) 3 ^ - [1- (4-Sch- (2-dimethylaminoethyl) -No-propionylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone: the said compound is obtained from 1-acetyl-3- ( 1-ethoxy-1-phenylmethylene) -6methoxycarbonyl-2-indolinone and 4-Shch- (2-dimethylaminoethyl) -N. propionylamino) aniline,

K-value: 0.5 (silica gel, methylene chloride / methanol 9: 1), 30 ^C ^Η 32 ^N 4 ^O ⁴ Mass Spectrum (E8TS: m / ζ = 511 [M-H ^-];

(73) 3 ^ - [1- (4-Sch- (2-dimethylaminoethyl) -N-butyrylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone: the said compound is obtained from 1-acetyl-3- ( 1-ethoxy-1-phenylmethylene) -6methoxycarbonyl-2-indolinone and 4-Sch- (2-dimethylaminoethyl) -N. butyrylamino) aniline,

K-value: 0.5 (silica gel, methylene chloride / methanol in a ratio of 9: 1),

- 46 006080 ^С 31 ^Н 34М ₄ ^О 4, mass spectrum (EM): t / ζ = 525 [M – H ^- ];

(74) 3-2- [1- (4-Shch- (2-dimethylaminoethyl) -N. Isobutyrylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone: said compound is obtained from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6methoxycarbonyl-2-indolinone and 4-Sch- (2-dimethylaminoethyl) -N, isobutyrylamino) aniline,

Purpose: 0.5 (silica gel, methylene chloride / methanol in a ratio of 9: 1), mass spectrum (EM): t / ζ = 525 [M – H ^- ];

(75) 3-2- [1- (4-Shch- (2-dimethylaminoethyl) -N.benzoylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone: said compound is obtained from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6methoxycarbonyl-2-indolinone and 4-Shch- (2-dimethylaminoethyl) -N. Benzoylamino) aniline,

H _g value: 0.5 (silica gel, methylene chloride / methanol 9: 1), ^C 34 ^Η 32 ^N 4 ^O 4 ^, mass spectrum (EM): t / ζ = 559 [M – H ^- ];

(76) 3 -Ζ- [1- (4- (C- (2-dimethylaminoethyl) -N acetylamino) -3-aminoanilino) -1-phenylmethylene] -6methoxycarbonyl-2-indolinone: this compound is obtained from 1-acetyl- 3- (1-ethoxy-1phenylmethylene) -6-methoxycarbonyl-2-indolinone and 4-Shch- (2-dimethylaminoethyl) -Noacetylamino) -3 aminoaniline,

Purpose: 0.5 (aluminum oxide, methylene chloride / methanol in a ratio of 20: 1), ^C 29 ^H 31M5 ^O 4, mass spectrum (EM): t / ζ = 512 [M – H ^- ];

(77) 3 -Ζ- [1 - (4- (4-hydroxymethylpiperidin-1-ylmethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone: said compound is obtained from 1-acetyl-3- (1 ethoxy-1-phenylmethylene) -6 methoxycarbonyl-2-indolinone and 4- (4-hydroxymethylpiperidin-1-ylmethylamino) aniline,

H _g value: 0.3 (silica gel, methylene chloride / methanol in the ratio 5: 1), ^С 30 ^Н 31П ₃ ^О 4, mass spectrum (ЕМ): t / ζ = 496 [М-Н ^- ];

(78) 3 ^ - [1- (4- (2- (4-hydroxypiperidin-1-yl) ethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl2-indolinone: said compound is obtained from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-methoxycarbonyl-2-indolinone and 4- (2- (4-hydroxypiperidin-1-yl) ethylamino) aniline,

H (-value: 0.3 (silica gel, methylene chloride / methanol 5: 1 ratio), ^C 30 ^H 31 ^P ₃ ^O 4, mass spectrum (EM): t / ζ = 496 [M – H ^- ];

(79) 3 ^ - [1- (4- (C- (2-dimethylaminoethyl) -Npropylsulfonylamino) anilino) -1-phenylmethylene] -6methoxycarbonyl-2-indolinone: this compound is obtained from 1-acetyl-3- (1 -ethoxy-1-phenylmethylene) -6-methoxycarbonyl-2-indolinone and No. (2-dimethylaminoethyl) -Npropylsulfonyl-p-phenylenediamine,

H _g value: 0.5 (silica gel, methylene chloride / methanol in the ratio 9: 1), ^C 30 ^H 34-No.4 ^O 5 ^?

mass spectrum (EM): t / ζ = 561 [M – H ^- ];

(80) 3 -Ζ- [1 - (4-Sch- (2-dimethylaminoethyl) -N.butylsulfonylamino) anilino) -1-phenylmethylene] -6methoxycarbonyl-2-indolinone: the compound is obtained from 1-acetyl-3- (1 -ethoxy-1phenylmethylene) -6-methoxycarbonyl-2-indolinone and No. (2-dimethylaminoethyl) -N. butylsulfonyl-pphenylenediamine,

H _g value: 0.5 (silica gel, methylene chloride / methanol in a ratio of 9: 1),

C31H ₃ 6CHO5M mass spectrum (EM): t / ζ = 575 [M – H ^- ];

(81) 3 ^ - [1- (4-Sch- (2-dimethylaminoethyl) -Hphenylsulfonylamino) anilino) -1-phenylmethylene] -6methoxycarbonyl-2-indolinone: this compound is obtained from 1-acetyl-3- (1- ethoxy-1phenylmethylene) -6-methoxycarbonyl-2-indolinone and no. (2-dimethylaminoethyl) -№ phenylsulfonyl-pphenylenediamine,

H _g value: 0.5 (silica gel, methylene chloride / methanol in a ratio of 9: 1),

C ^ H ^ OzM mass spectrum (EM): t / ζ = 595 [M – H ^- ];

(82) 3 -Ζ- [1 - (4-Sch- (2-dimethylaminoethyl) -Nobenzylsulfonylamino) anilino) -1-phenylmethylene] -6methoxycarbonyl-2-indolinone: this compound is obtained from 1-acetyl-3- (1 -ethoxy-1-phenylmethylene) -6-methoxycarbonyl-2-indolinone and No. (2-dimethylaminoethyl) -N.benzylsulfonyl-p-phenylenediamine,

H _g value: 0.5 (silica gel, methylene chloride / methanol in a ratio of 9: 1),

С ₃₄ Н ₃₄ ЩО ₅ М mass spectrum (ЕМ): t / ζ = 609 [М-Н ^- ];

- 47 006080 (83) 3 ^ - [1- (4- (No. (2-dimethylaminoethyl) -Noethylsulfonylamino) anilino) -1-phenylmethylene] -6methoxycarbonyl-2-indolinone: this compound is obtained from 1-acetyl-3- (1-ethoxy-1phenylmethylene) -6-methoxycarbonyl-2-indolinone and No. (2-dimethylaminoethyl) -Noethylsulfonyl-pphenylenediamine,

H _g value: 0.5 (silica gel, methylene chloride / methanol in the ratio 9: 1), mass spectrum (EM): t / ζ = 547 [M – H ^- ];

(84) 3 ^ - [1- (4 - ((imidazolidin-2,4-dione-5-yl) methyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl2-indolinone: this compound is obtained from 1-acetyl- 3- (1-ethoxy-1-phenylmethylene) -6-methoxycarbonyl-2-indolinone and 4 - ((imidazolidin-2,4-dione-5-yl) methyl) aniline,

K-value: 0.6 (silica gel, methylene chloride / methanol in the ratio 5: 1), ^C 2 ₇ H22 ^ O5, mass spectrum (EM): t / ζ = 481 [M – H ^- ];

(85) 3 -Ζ- [1 - (4 - ((3 -hydroxypyrrolidin-1-yl) methyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl2-indolinone: this compound is obtained from 1-acetyl-3- ( 1-ethoxy-1-phenylmethylene) -6-methoxycarbonyl-2-indolinone and 4 - (((3-hydroxypyrrolidin-1-yl) methyl) aniline,

K-value: 0.1 (silica gel, methylene chloride / methanol in the ratio 10: 1), ^C 28 ^H 27 ^ ^O 4, mass spectrum (EM): t / ζ = 468 [M – H ^- ];

(86) 3 -Ζ- [1- (4- (cyclohexylmethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone: the compound is obtained from 1-acetyl-3- (1-ethoxy-1-phenylmethylene ) -6-methoxycarbonyl-2 indolinone and 4- (cyclohexylmethyl) aniline (Eig. I. Meb. Syet. Sygt. Tyer. 27: 537-544 (1992)),

Purpose: 0.6 (silica gel, methylene chloride / methanol in a ratio of 10: 1), ^C 30 He0 ^ O ₃ , mass spectrum (EM): t / ζ = 465 [M – H ^- ];

(87) 3 ^ - [1- (4- (cyclohexylcarbonyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone: the title compound is obtained from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-methoxycarbonyl-2-indolinone and 4- (cyclohexylcarbonyl) aniline,

H _g value: 0.5 (silica gel, methylene chloride / methanol in a ratio of 10: 1), ^C 30 ^H 28 ^N 2 ^O 4 ^, mass spectrum (EM): t / ζ = 479 [M – H ^- ];

(88) 3 ^ - [1- (4-diethylaminomethylanilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone: this compound is obtained from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6- methoxycarbonyl-2 indolinone and 4- (diethylaminomethyl) aniline,

H _g value: 0.4 (silica gel, methylene chloride / methanol in a ratio of 10: 1), ^C 28 H29 ^ O ₃ , mass spectrum (EM): t / ζ = 454 [M – H ^- ];

(89) 3 -Ζ- [1 - (4- (No. (n-hexyl) -Nomethylaminomethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2indolinone: said compound is obtained from 1-acetyl-3- (1 -ethoxy-1-phenylmethylene) -6-methoxycarbonyl-2-indolinone and 4- (No. (p-hexyl) -Nomethylaminomethyl) aniline,

Purpose: 0.6 (silica gel, methylene chloride / methanol in a ratio of 10: 1),

C ₃ 1H ₃ 5 ^ O ₃ , mass spectrum (EM): t / ζ = 496 [M – H ^- ];

(90) 3 -Ζ- [1 - (4- (No. (2-dimethylaminoethyl) -N (furan-2-carbonyl) amino) anilino) -1-phenylmethylene] -6 methoxycarbonyl-2-indolinone: the compound is obtained from 1 -acetyl-3- (1-ethoxy-1-phenylmethylene) -6-methoxycarbonyl-2-indolinone and 4- (No. (2-dimethylaminoethyl) -N (furan-2-carbonyl) amino) aniline,

H _g value: 0.5 (silica gel, methylene chloride / methanol in a ratio of 9: 1), ^C 32 ^H 30 ^N 4 ^O 5 ^, mass spectrum (EM): t / ζ = 549 [M – H ^- ];

(91) 3 ^ - [1- (4- (No. (2-dimethylaminoethyl) -N (2-methoxybenzoyl) amino) anilino) -1-phenylmethylene] -6 methoxycarbonyl-2-indolinone: this compound is obtained from 1-acetyl- 3- (1-ethoxy-1-phenylmethylene) -6-methoxycarbonyl-2-indolinone and 4- (No. (2-dimethylaminoethyl) -N (2-methoxybenzoyl) amino) aniline,

Purpose: 0.5 (silica gel, methylene chloride / methanol in a ratio of 9: 1), ^C 35 ^H 34 ^N 4 ^O 5 ^, mass spectrum (EM): t / ζ = 589 [M – H ^- ];

(92) 3 -Ζ- [1 - (4- (No. (2-dimethylaminoethyl) -N (pyridine-3-carbonyl) amino) anilino) -1-phenylmethylene] 6-methoxycarbonyl-2-indolinone: this compound is obtained from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-methoxycarbonyl-2-indolinone and 4- (No. (2-dimethylaminoethyl) -N (pyridine-3-carbonyl) amino) aniline,

H _g value: 0.5 (silica gel, methylene chloride / methanol in a ratio of 9: 1),

- 48 006080 ^С 33 ^Н 31№ ^О 4, mass spectrum (ЕМ): t / ζ = 560 [М-Н ^- ];

(93) 3-2- [1- (4- (No. (2-dimethylaminoethyl) -N (phenylacetyl) amino) anilino) -1-phenylmethylene] -6 methoxycarbonyl-2-indolinone: this compound is obtained from 1-acetyl-3 - (1-ethoxy-1-phenylmethylene) -6-methoxycarbonyl-2-indolinone and 4- (No. (2-dimethylaminoethyl) -N (phenylacetyl) amino) aniline,

K-value: 0.5 (silica gel, methylene chloride / methanol in the ratio 9: 1), ^C 35 ^Η 34 ^N 4 ^O 4 ^, mass spectrum (EM): t / ζ = 573 [M – H ^- ];

(94) 3-2- [1- (4- (#ethyl-No.methylaminomethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone: this compound is obtained from 1-acetyl-3- (1-ethoxy -1-phenylmethylene) -6-methoxycarbonyl-2 indolinone and 4- (No. ethyl-No. methylaminomethyl) aniline,

K-value: 0.3 (silica gel, methylene chloride / methanol = 10: 1), 27 ^C ^Η 27 ^N 3 ^O ³ MS (EM): m / ζ = 440 [M-H ^-];

(95) 3-2- [1- (4- (imidazol-2-yl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone: said compound is obtained from 1-acetyl-3- (1-ethoxy -1-phenylmethylene) -6-methoxycarbonyl-2-indolinone and 4- (imidazol-2-yl) aniline,

K-value: 0.5 (silica gel, methylene chloride / methanol in a ratio of 10: 1),

C26H20 ^ Oe, mass spectrum (EM): t / ζ = 435 [M – H ^- ];

(96) 3 -Ζ- [1- (4- (1-ethylimidazol-2-yl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone: this compound is obtained from 1-acetyl-3- (1 ethoxy-1-phenylmethylene) -6-methoxycarbonyl-2indolinone and 4- (1-ethylimidazol-2-yl) aniline,

K-value: 0.4 (silica gel, methylene chloride / methanol in the ratio 10: 1), ^C 28 ^Η 24 ^N 4 ^O 3 ^, mass spectrum (EM): t / ζ = 463 [M-H ^- ];

(97) 3-Ζ- [1- (4- (1-benzylimidazol-2-yl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone: said compound is obtained from 1-acetyl-3- (1 ethoxy-1-phenylmethylene) -6-methoxycarbonyl-2 indolinone and 4- (1-benzylimidazol-2-yl) aniline,

K-value: 0.3 (silica gel, methylene chloride / methanol in a ratio of 20: 1),

SE3H26 # Oe, mass spectrum (EM): t / ζ = 525 [M – H ^- ];

(98) 3 ^ - [1- (4- (No. (2-dimethylaminoethyl) -№ Isopropylsulfonylamino) anilino) -1-phenylmethylene] 6-methoxycarbonyl-2-indolinone: this compound is obtained from 1-acetyl-3- (1 -ethoxy-1phenylmethylene) -6-methoxycarbonyl-2-indolinone and No. (2-dimethylaminoethyl) -N isopropylsulfonyl-phenylenediamine

K-value: 0.5 (silica gel, methylene chloride / methanol in the ratio 9: 1), ^C 30 ^H 34- ^No . 4 ^O 5 ^.

mass spectrum (EM): t / ζ = 561 [M – H ^- ];

(99) 3 -Ζ- [1 - (4- (no. (Piperidin-1-ylmethylcarbonyl) -Nomethylamino) anilino) -1-phenylmethylene] -6methoxycarbonyl-2-indolinone: this compound is obtained from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-methoxycarbonyl-2-indolinone and No. (piperidin-1-ylmethylcarbonyl) -№ methyl-p-phenylenediamine,

K-value: 0.5 (silica gel, methylene chloride / methanol in the ratio 9: 1), ^C 31 ^H 32 No. ^O 4, mass spectrum (EM): t / ζ = 523 [M – H ^- ];

(100) 3 ^ - [1- (4- (No. (morpholin-4-ylmethylcarbonyl) -Nomethylamino) anilino) -1-phenylmethylene] -6methoxycarbonyl-2-indolinone: this compound is obtained from 1-acetyl-3- ( 1-ethoxy-1phenylmethylene) -6-methoxycarbonyl-2-indolinone and no. (Morpholin-4-ylmethylcarbonyl) -№ methyl-phenylenediamine,

K-value: 0.5 (silica gel, methylene chloride / methanol in a ratio of 9: 1),

Ce0Ne0 # O5, mass spectrum (EM): t / ζ = 525 [M – H ^- ];

(101) 3 ^ - [1- (4- (No. ((4-benzylpiperazin-1-yl) methylcarbonyl) -Nmethylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone: this compound is obtained from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-methoxycarbonyl-2-indolinone and No. ((4-benzylpiperazin-1-yl) methylcarbonyl) -N methyl-p-phenylenediamine,

K-value: 0.5 (silica gel, methylene chloride / methanol in the ratio 9: 1), ^C 37 ^H 37 No. ^O 4, mass spectrum (EM): t / ζ = 614 [M – H ^- ];

- 49 006080 (102) 3 -Ζ - [1 - (4- (no. (Pyrrolidin-1-ylmethylcarbonyl) -Y-methylamino) anilino) -1-phenylmethylene] -6methoxycarbonyl-2-indolinone: said compound is obtained from 1- acetyl-3- (1-ethoxy-1-phenylmethylene) -6-methoxycarbonyl-2-indolinone and no. (pyrrolidin-1-ylmethylcarbonyl) -Y-methyl-p-phenylenediamine,

K _d value: 0.5 (silica gel, methylene chloride / methanol 9: 1), 30 ^C ^Η 30 ^N 4 ^O ⁴ Mass Spectrum (E8TS: m / ζ = 509 [M-H ^-];

(103) 3 ^ - [1- (4- (K- (2-dimethylaminoethyl) -Y-acetylamino) -3-bromoanilino) -1-phenylmethylene] -6methoxycarbonyl-2-indolinone: this compound is obtained from 1-acetyl- 3- (1-ethoxy-1phenylmethylene) -6-methoxycarbonyl-2-indolinone and 4- (No. (2-dimethylaminoethyl) -Y-acetylamino) -3 bromoaniline,

K _g value: 0.6 (silica gel, methylene chloride / methanol 5: 1),

С29Η29ΒГN4О4, mass spectrum (Е8Ц: t / ζ = 575/577 [М-Н ^- ];

(104) 3 -Ζ- [1- (4- (5-methylimidazol-4-yl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone: this compound is obtained from 1-acetyl-3- (1 ethoxy-1-phenylmethylene) -6-methoxycarbonyl-2indolinone and 4- (5-methylimidazol-4-yl) aniline,

K-value: 0.5 (silica gel, methylene chloride / methanol / ammonia in a ratio of 10: 1: 0.01),

C ^ H ^ PdOz, mass spectrum (E8C: t / ζ = 449 [M – H ^- ];

(105) 3 -Ζ- [1 - (4- (No. ((2-dimethylaminoethyl) carbonyl) -Y-isopropylamino) anilino) -1-phenylmethylene] 6-methoxycarbonyl-2-indolinone: this compound is obtained from 1-acetyl -3- (1-ethoxy-1phenylmethylene) -6-methoxycarbonyl-2-indolinone and No. ((2-dimethylaminoethyl) carbonyl) -Y-isopropyl-pphenylenediamine,

To _g value: 0.1 (silica gel, methylene chloride / methanol in a ratio of 10: 1),

Sz1H ₃₄ ^ O4, mass spectrum (E8Ts: t / ζ = 525 [M – H];

(106) 3 -Ζ- [1- (4- (K - ((2-dimethylaminoethyl) carbonyl) -Y-benzylamino) anilino) -1-phenylmethylene] -6 methoxycarbonyl-2-indolinone: this compound is obtained from 1-acetyl -3- (1-ethoxy-1-phenylmethylene) -6-methoxycarbonyl-2-indolinone and NO (((2-dimethylaminoethyl) carbonyl) -Y-benzyl-p-phenylenediamine,

K-value: 0.1 (silica gel, methylene chloride / methanol in the ratio 10: 1), ^С 31 ^Н 3 ₄ М ₄ ^О 4, mass spectrum (Е8Ц: t / ζ = 525 [М-Н ^- ];

(107) 3 ^ - [1- (4- (No. butyl-N-tert-butoxycarbonylaminomethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone: the compound is obtained from 1-acetyl-3- (1 ethoxy-1-phenylmethylene) -6 methoxycarbonyl-2-indolinone and 4- (No. butyl-N-tert-butoxycarbonylaminomethyl) aniline,

To _g value: 0.5 (silica gel, methylene chloride / methanol in a ratio of 9: 1),

С ₃₃ Н ₃₇ № (О5, mass spectrum (Е8Ц: t / = 554 [М-Н ^- ];

(108) 3 ^ - [1- (4- (No. ((Aminocarbonylmethyl-Y-methylamino) methylcarbonyl) -Y-methylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone: the compound is obtained from 1-acetyl-3 (1-ethoxy-1-phenylmethylene) -6-methoxycarbonyl-2-indolinone and No. (No. aminocarbonylmethyl-N-methylamino) methylcarbonyl) -Y-methyl-p-phenylenediamine,

Kg value: 0.5 (silica gel, methylene chloride / methanol 9: 1),

C29H29 ^ O5, mass spectrum (E8C: t / ζ = 526 [M – H ^- ];

(109) 3 -Ζ- [1 - (4- (No. ((No.benzyl-N-methylamino) methylcarbonyl) -Y-methylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone: the specified connection receive from 1-acetyl-3- (1-ethoxy-1phenylmethylene) -6-methoxycarbonyl-2-indolinone and No. ((No.benzyl-N-methylamino) methylcarbonyl) -Ymethyl-p-phenylenediamine,

K-value: 0.5 (silica gel, methylene chloride / methanol in the ratio 9: 1), ^C 34 ^N 32P4 ^O 4?

mass spectrum (E8C: t / = 559 [M – H ^- ];

(110) 3 ^ - [1- (4- (K- (di- (2-methoxyethyl) aminomethylcarbonyl) -Y-methylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone: said compound is obtained from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-methoxycarbonyl-2-indolinone and No. (di (2-methoxyethyl) aminomethylcarbonyl) -Ymethyl-p-phenylenediamine,

K _g value: 0.5 (silica gel, methylene chloride / methanol in the ratio 9: 1), ^C 32 ^Η 36 ^N 4 ^O 6 ^, mass spectrum (Е8Ц: t / ζ = 571 [M – H ^- ];

- 50 006080 (111) 3-Ζ- [1 - (4- (K - ((2- (4-tert-butoxycarbonylpiperazin-1-yl) ethyl) carbonyl) -M-methylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone: the compound is obtained from 1 acetyl-3 - (1-ethoxy-1-phenylmethylene) -6-methoxycarbonyl-2-indolinone and N - (((2- (4-tert-butoxycarbonylpiperazin-1 - (yl) ethyl) carbonyl) -Y-methyl-p-phenylenediamine, ^ (- value: 0.8 (silica gel, methylene chloride / methanol in the ratio 5: 1), mass spectrum (ЕЕ): t / ζ = 638 [M -H ^- ];

(112) 3 -Ζ- [1 - (4- (M - ((2- (piperidin-1-yl) ethyl) carbonyl) -M-methylamino) anilino) -1-phenylmethylene] 6-methoxycarbonyl-2-indolinone : the compound is obtained from 1-acetyl-3- (1-ethoxy-1phenylmethylene) -6-methoxycarbonyl-2-indolinone and M - ((2- (piperidin-1-yl) ethyl) carbonyl) -N-methyl-phenylindiamine ,

I-value: 0.5 (silica gel, methylene chloride / methanol in the ratio 5: 1),

^Η ^Ν 032 34 4 4 ^Ο, MS (EE): m / ζ = 537 [M-H ^-];

(113) 3 -Ζ- [1 - (4- (L - ((2- (K-benzyl-N-methylamino) ethyl) carbonyl) -H-methylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl- 2-indolinone: the compound is obtained from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-methoxycarbonyl-2-indolinone and M - ((2- (M-benzyl-M-methylamino) ethyl) carbonyl) - Mmethyl-p-phenylenediamine,

K-value: 0.4 (silica gel, methylene chloride / methanol in a ratio of 10: 1),

^Η ^Ν 035 34 4 4 ^Ο, MS (EE): m / ζ = 573 [M-H ^-];

(114) 3 ^ - [1- (4- (K-dimethylaminomethylcarbonyl-H-isopropylamino) anilino) -1-phenylmethylene] -6methoxycarbonyl-2-indolinone: this compound is obtained from 1-acetyl-3- (1-ethoxy- 1phenylmethylene) -6-methoxycarbonyl-2-indolinone and M- (dimethylaminomethylcarbonyl) -M-isopropyl-phenylenediamine,

I-value: 0.5 (silica gel, methylene chloride / methanol in a ratio of 9: 1),

6'30 ^Η 32 ^Ν 4 ^Ο 4, mass spectrum (EE): t / ζ = 511 [M – H ^- ];

(115) 3-Ζ- [1- (4- (M- (piperidin-1-ylmethylcarbonyl) -M-isopropylamino) anilino) -1-phenylmethylene] 6-methoxycarbonyl-2-indolinone: said compound is obtained from 1-acetyl -3- (1-ethoxy-1phenylmethylene) -6-methoxycarbonyl-2-indolinone and N- (piperidin-1 -ylmethylcarbonyl) -M-isopropyl-pphenylenediamine,

Е _g value: 0.5 (silica gel, methylene chloride / methanol in the ratio 9: 1), ^ 3 ^ 4 ^ mass spectrum (ЕЕ): t / ζ = 551 [M – H ^- ];

(116) 3 -Ζ- [1 - (4- (M - ((4-tert-butoxycarbonylpiperazin-1-yl) methylcarbonyl) -M-isopropylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone : the compound is obtained from 1 acetyl-3 - (1-ethoxy-1-phenylmethylene) -6-methoxycarbonyl-2-indolinone and Y - (((4-tert-butoxycarbonylpiperazin-1-yl) methylcarbonyl) -M-isopropyl-p- Phenylenediamine, ^ {- value: 0.5 (silica gel, methylene chloride / methanol in the ratio 9: 1), mass spectrum (EE): t / ζ = 652 [M – H ^- ];

(117) 3 ^ - [1- (4- (L - ((K-benzyl-N-methylamino) methylcarbonyl) -H-benzylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone: the specified connection get from 1-acetyl-3- (1-ethoxy-1phenylmethylene) -6-methoxycarbonyl-2-indolinone and M - ((M-benzyl-M-methylamino) methylcarbonyl) -Mbenzyl-p-phenylenediamine,

I-value: 0.5 (silica gel, methylene chloride / methanol in the ratio 9: 1), ^ 0 ^ 6 ^ 04, mass spectrum (ЕЕ): t / ζ = 635 [M – H ^- ];

(118) 3-Ζ- [1 - (4- (L-dimethylaminomethylcarbonyl-H-benzylamino) anilino) -1-phenylmethylene] -6 methoxycarbonyl-2-indolinone: the compound obtained is obtained from 1-acetyl-3- (1-ethoxy -1phenylmethylene) -6-methoxycarbonyl-2-indolinone and N- (dimethylaminomethylcarbonyl) -H-benzyl-phenylenediamine,

Е _g value: 0.5 (silica gel, methylene chloride / methanol in the ratio 9: 1), ^ 4 ^ 2 ^ ¾ mass spectrum (ЕЕ): t / = 559 [M – H ^- ];

(119) 3 -Ζ- [1- (4- (L- (piperidin-1-ylmethylcarbonyl) -H-benzylamino) anilino) -1-phenylmethylene] -6methoxycarbonyl-2-indolinone: this compound is obtained from 1-acetyl- 3- (1-ethoxy-1-phenylmethylene) -6-methoxycarbonyl-2-indolinone and 4- (5-methylimidazol-4-yl) aniline,

I-value: 0.5 (silica gel, methylene chloride / methanol in a ratio of 9: 1),

6'37 ^Η 36 ^Ν 4 ^Ο 4, MS (EE): m / ζ = 559 [M-H ^-];

- 51 006080 (120) 3 -Ζ- [1 - (4- (1,2,4-triazol-2-ylmethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone: said compound is obtained from 1 -acetyl-3- (1-ethoxy-1-phenylmethylene) -6-methoxycarbonyl-2 indolinone and 4- (1,2,4-triazol-1-ylmethyl) aniline,

In _g value: 0.5 (silica gel, methylene chloride / methanol in a ratio of 10: 1),

Su.kUD, mass spectrum (E8TS t / ζ = 450 [M – H ^- ];

(121) 3 -Ζ- [1- (4- (1,2,3-triazol-2-ylmethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone: this compound is obtained from 1-acetyl- 3- (1-ethoxy-1-phenylmethylene) -6-methoxycarbonyl-2indolinone and 4- (1,2,3-triazol-2-ylmethyl) aniline,

The value: 0.5 (silica gel, methylene chloride / methanol in a ratio of 20: 1),

66¾¾¾ mass spectrum (Е8Ц t / = 450 [M – H ^- ];

(122) 3 -Ζ- [1- (4- (1,2,3-triazol-1-ylmethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone: this compound is obtained from 1-acetyl- 3- (1-ethoxy-1-phenylmethylene) -6-methoxycarbonyl-2 indolinone and 4- (1,2,3-triazol-1-ylmethyl) aniline,

In _g value: 0.4 (silica gel, methylene chloride / methanol 9: 1),

Su.kUD, mass spectrum (E8TS t / ζ = 450 [M – H ^- ];

(123) 3-Ζ- [1 - (4 - ((Aminocarbonylmethyl-No.methylamino) methyl) anilino) -1-phenylmethylene] -6methoxycarbonyl-2-indolinone: this compound is obtained from 1-acetyl-3- (1- ethoxy-1-phenylmethylene) -6-methoxycarbonyl-2-indolinone and 4 - ((No. aminocarbonylmethyl-No.methylamino) methyl) aniline,

The value: 0.5 (silica gel, methylene chloride / methanol in the ratio 9: 1), ^C 27 ^Η 26 ^N 4 ^O 4 ^, mass spectrum (E 8C t / = 469 [M – H ^- ];

(124) 3 -Ζ- [1 - (4 - ((di- (2-methoxyethyl) amino) methyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2indolinone: this compound is obtained from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-methoxycarbonyl-2-indolinone and 4 - ((di (2-methoxyethyl) amino) methyl) aniline,

In _g value: 0.5 (silica gel, methylene chloride / methanol in the ratio 9: 1), ^С 30 ^Η 33 ^N 3 ^О 5 ^, mass spectrum (Е8Ц t / ζ = 514 [М-Н ^- ];

(125) 3 -Ζ- [1- (4- (pyrrolidin-1-ylmethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone: this compound is obtained from 1-acetyl-3- (1-ethoxy -1-phenylmethylene) -6-methoxycarbonyl-2 indolinone and 4- (pyrrolidin-1-ylmethyl) aniline,

The value: 0.5 (silica gel, methylene chloride / methanol in the ratio 9: 1), ^С 28Н27 ^ О3, mass spectrum (Е8Ц t / ζ = 452 [М-Н ^- ];

(126) 3 -Ζ- [1- (4 - ((di- (2-hydroxyethyl) amino) methyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl2-indolinone: this compound is obtained from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6methoxycarbonyl-2-indolinone and 4 - ((di (2-hydroxyethyl) amino) methyl) aniline,

In _g value: 0.5 (silica gel, methylene chloride / methanol in a ratio of 9: 1),

C28H29 ^ O5, mass spectrum (Е8Ц t / = 486 [Μ-Η ^- ];

(127) 3-Ζ- [1 - (4 - ((ethoxycarbonylmethyl-No.methylamino) methyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone: this compound is obtained from 1-acetyl-3- ( 1-ethoxy-1-phenylmethylene) -6methoxycarbonyl-2-indolinone and 4 - ((No. of ethoxycarbonylmethyl-No.methylamino) methyl) aniline,

B value: 0.5 (aluminum oxide, methylene chloride / ethanol in the ratio of 40: 1), mass spectrum (E8C t / ζ = 498 [M – H ^- ];

(128) 3-Ζ- [1- (4- (azetidin-1-methylmethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone: the compound is obtained from 1-acetyl-3- (1-ethoxy -1-phenylmethylene) -6-methoxycarbonyl-2-indolinone and 4- (azetidin-1-ylmethyl) aniline,

The value: 0.5 (silica gel, methylene chloride / methanol / ammonia in a ratio of 9: 1: 0.5),

C27Η25N3O3, mass spectrum (E8C t / ζ = 438 [M – H ^- ];

(129) 3 -Ζ- [1- (4- (No.propyl-No.t-butoxycarbonylaminomethyl) anilino) -1-phenylmethylene] -6methoxycarbonyl-2-indolinone: the compound obtained is obtained from 1-acetyl-3- (1-ethoxy -1-phenylmethylene) -6-methoxycarbonyl-2-indolinone and 4- (No.propyl-No.t-butoxycarbonylaminomethyl) aniline,

In _g value: 0.5 (silica gel, methylene chloride / methanol in the ratio 9: 1), ^C 32 ^Η 35 ^N 3 ^O 5 ^, mass spectrum (Е8Ц t / ζ = 540 [М-Н ^- ];

- 52 006080 (130) 3 -Ζ- [1 - (4 ((no. (2- (2-methoxyethoxy) ethyl) -H-methylamino) methyl) anilino) -1-phenylmethylene] -6 methoxycarbonyl-2-indolinone: indicated The compound is obtained from 3-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-methoxycarbonyl-2-indolinone and 4 - ((No. (2- (2-methoxyethoxy) ethyl) -I-methylamino) methyl) aniline ,

K _{ -value: 0.4 (silica gel, methylene chloride / methanol 9: 1), ^C 30 ^Η 33 ^N 3 ^O 5 ^, mass spectrum (EM): t / ζ = 514 [M – H ^- ];

(131) 3 ^ - [1- (4 - ((no. (Tert-butoxycarbonyl-3-aminopropyl) -Y-methylamino) methyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone: said compound is obtained from 1-acetyl-3- (1-ethoxy-1phenylmethylene) -6-methoxycarbonyl-2-indolinone and 4- (No. (No. tert-butoxycarbonyl-3-aminopropyl) -Ymethylaminomethyl) aniline,

K {-value: 0.5 (silica gel, methylene chloride / methanol 9: 1),

C33H38N4O5, ₊ mass spectrum (EM): t / ζ = 571 [M + H ⁺ ];

(132) 3 -Ζ - [1 - (4 - ((no. (Methylcarbamoylmethyl) -I-methylamino) methyl) anilino) -1-phenylmethylene] -6methoxycarbonyl-2-indolinone: this compound is obtained from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-methoxycarbonyl-2-indolinone and 4 - ((No. (methylcarbamoylmethyl) -I-methylamino) methyl) aniline,

{K -value: 0,5 (silica gel, methylene chloride / methanol 9: 1), 28 ^C ^Η 28 ^N 4 ^O ⁴ Mass Spectrum (EM): m / ζ = 483 [M-H ^-];

(133) 3 -Ζ - [1 - (4 - ((no. (Dimethylcarbamoylmethyl) -H-methylamino) methyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone: this compound is obtained from 1-acetyl- 3- (1-ethoxy-1phenylmethylene) -6-methoxycarbonyl-2-indolinone and 4 - ((No. (dimethylcarbamoylmethyl) -Ymethylamino) methyl) aniline,

K _{ -value: 0.3 (silica gel, methylene chloride / methanol 10: 1), ^C 29 ^Η 30 ^N 4 ^O 4 ^, mass spectrum (EM): t / ζ = 497 [M – H ^- ];

(134) 3 ^ - [1- (4-methylanilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone: this compound is obtained from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6- methoxycarbonyl-2-indolinone and 4methylaniline,

K {-value: 0.4 (silica gel, methylene chloride / methanol 9: 1),

C24H20 ^ O ₃ , mass spectrum (EM): t / ζ = 383 [M – H ^- ];

(135) 3-Ζ- [1- (4 - ((No.propyl-N-methylamino) methyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2indolinone: the compound is obtained from 1-acetyl-3- (1 ethoxy-1-phenylmethylene) -6-methoxycarbonyl-2-indolinone and 4 - ((N-propyl-N-methylamino) methyl) aniline,

_{K -value: 0,5 (silica gel, methylene chloride / methanol 9: 1), 28 ^C ^Η 29 ^N 3 ^O ³ MS (EM): m / ζ = 454 [M-H ^-];

(136) 3 -Ζ- [1- (4 - ((no. (2-hydroxyethyl) -I-methylamino) methyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone: said compound is obtained from 1- acetyl-3- (1-ethoxy-1-phenylmethylene) -6methoxycarbonyl-2-indolinone and 4 - ((L- (2-hydroxyethyl) -H-methylamino) methyl) aniline,

K-value: 0.5 (aluminum oxide, methylene chloride / ethanol in the ratio 40: 1), ^C 27 ^H 27 ^ ^O + mass spectrum (EM): t / ζ = 456 [M – H ^- ];

(137) 3 -Ζ - [1 - (4 - ((No. (2-dimethylaminoethyl) -Y-methylamino) methyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone: this compound is obtained from 1- acetyl-3- (1-ethoxy-1-phenylmethylene) -6-methoxycarbonyl-2-indolinone and 4 - ((no (2-dimethylaminoethyl) -Y-methylamino) methyl) aniline,

K _{ -value: 0.5 (silica gel, methylene chloride / methanol 9: 1),

C29Ne2 ^ Oe, mass spectrum (EM): t / ζ = 483 [M – H ^- ];

(138) 3 ^ - [1- (4 - ((no. (3-dimethylaminopropyl) -H-methylamino) methyl) anilino) -1-phenylmethylene] -6methoxycarbonyl-2-indolinone: this compound is obtained from 1-acetyl-3 - (1-ethoxy-1phenylmethylene) -6-methoxycarbonyl-2-indolinone and 4 - ((Ν- (3-dimethylaminopropyl) -Y-methylamino) methyl) aniline,

K _{ -value: 0.5 (silica gel, methylene chloride / methanol 9: 1),

C30H34 ^ Oe, mass spectrum (EM): t / ζ = 497 [M – H ^- ];

- 53 006080 (139) 3 -Ζ- [1- (4- (3-oxopiperazin-1-ylmethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2 indolinone: the compound is obtained from 1-acetyl-3- ( 1-ethoxy-1-phenylmethylene) -6-methoxycarbonyl-2-indolinone and 4- (3-oxopiperazin-1-ylmethyl) aniline,

K-value: 0.46 (silica gel, methylene chloride / methanol in a ratio of 9: 1), ^C 28 ^H 26 ^N 4 ^O 4 ^, mass spectrum (EM): t / ζ = 481 [M – H ^- ].

Example 4. 3 ^ - [1- (4-carboxyanilino) -1-phenylmethylene 1-6-ethoxycarbonyl-2-indolinone.

485 mg of 3 ^ - [1- (4-tert-butoxycarbonylanilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone is dissolved in 15 ml of methylene chloride and 6.0 ml of trifluoroacetic acid are added. The mixture is stirred for 2 hours at room temperature. The solvent is distilled off and the residue is recrystallized from ether.

Yield: 375 mg (87% of theory),

K-value: 0.3 (silica gel, methylene chloride / methanol in a ratio of 10: 1),

C25H20H2O5, mass spectrum: t / ζ = 428 [M ⁴ ].

Analogously to example 4 receive the following compounds:

(1) 3 -Ζ- [1- (4-aminomethylanilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone: this compound is obtained from 3 ^ - [1- (4- (M-tert-butoxycarbonylaminomethyl) anilino ) -1-phenylmethylene] -6methoxycarbonyl-2-indolinone,

K-value: 0.5 (silica gel, methylene chloride / methanol / ammonia in the ratio 5: 1: 0.01),

C24H21M ₃ O3, mass spectrum (EM): t / ζ = 398 [M – H ^- ];

(2) 3 -Ζ- [1- (4-ethylaminomethylanilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone: the indicated compound is obtained from 3 ^ - [1- (4- (L-tert-butoxycarbonylethylaminomethyl) anilino ) -1phenylmethylene] -6-methoxycarbonyl-2-indolinone,

K-value: 0.4 (silica gel, methylene chloride / methanol / ammonia in the ratio 10: 1: 0.01), ^C 26 ^H 25 ^N 3 ^O 3 ^, mass spectrum (EM): t / ζ = 426 [M- H ^- ];

(3) 3 ^ - [1- (4-carboxymethylanilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone: the title compound is obtained from 3 ^ - [1- (4-tert-butoxycarbonylmethylanilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone,

K-value: 0.1 (alumina, methylene chloride / ethanol / ammonia in a ratio of 5: 1: 0.01),

C26H22X2O5, mass spectrum (EM): t / ζ = 441 [M – H ^- ];

(4) 3 ^ - [1- (4-carboxyanilino) -1-ethylmethylene] -6-ethoxycarbonyl-2-indolinone: this compound is obtained from 3 ^ - [1- (4-tert-butoxycarbonylanilino) -1-ethylmethylene] -6-ethoxycarbonyl-2-indolinone,

K-value: 0.1 (aluminum oxide, methylene chloride / ethanol in a ratio of 20: 1), mass spectrum (EM): t / ζ = 379 [M-H ^- ];

(5) 3 -Ζ- [1- (4- (piperazin-1-ylmethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone: this compound is obtained from 3 ^ - [1- (4- ( 4-tert-butoxycarbonylpiperazin-1-ylmethyl) anilino) -1phenylmethylene] -6-methoxycarbonyl-2-indolinone,

K-value: 0.1 (silica gel, methylene chloride / methanol / ammonia in a ratio of 10: 1: 0.01),

C28H28X ~ 4O ₃ , mass spectrum (EM): t / ζ = 469 [M + H ⁺ ];

(6) 3 -Ζ- [1 - (4-butylaminomethylanilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone: the compound is obtained from 3 ^ - [1- (4- (M-butyl-N-tert -butoxycarbonylaminomethyl) anilino) -1phenylmethylene] -6-methoxycarbonyl-2-indolinone,

K-value: 0.5 (silica gel, methylene chloride / methanol in the ratio 9: 1), ^C 28 ^H 29 ^N 3 ^O 3 ^, mass spectrum (EM): t / ζ = 454 [M – H ^- ];

(7) 3 -Ζ- [1- (4-ethylaminomethylanilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone: the indicated compound is obtained from 3 ^ - [1- (4- (M-tert-butoxycarbonyl-H -ethylaminomethyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone,

K-value: 0.3 (silica gel, methylene chloride / methanol / ammonia in a ratio of 10: 1: 0.01),

C27H27M ₃ O ₃ , mass spectrum (EM): t / ζ = 442 [M + H ⁺ ];

(8) 3 ^ - [1- (4-ethylaminomethylanilino) -1-phenylmethylene] -6-carbamoyl-2-indolinone: the indicated compound is obtained from 3 ^ - [1- (4- (M-tert-butoxycarbonylethylaminomethyl) anilino) -1-phenylmethylene] -6carbamoyl-2-indolinone,

K-value: 0.2 (silica gel, methylene chloride / methanol / ammonia in the ratio 5: 1: 0.01),

- 54 006080 ^С 25 ^Η 24 ^N 4 ^О 2 ^, mass spectrum (EI): t / ζ = 411 [M – H ^- ];

(9) 3 -Ζ- [1- (4- (K (piperazin-1-ylmethylcarbonyl) -N isopropylamino) anilino) -1-phenylmethylene] -6methoxycarbonyl-2-indolinone: the said compound is obtained from 3 ^ - [1- (4- (K ((4-tert-butoxycarbonylpiperazin-1 -yl) methylcarbonyl) -Kisopropylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone,

K-value: 0.35 (silica gel, methylene chloride / methanol in the ratio 9: 1), ^C 32 ^Η 35 ^N 5 ^O 4 ^, mass spectrum (EI): t / ζ = 552 [M – H ^- ];

(10) 3-Ζ- [1- (4- (No. ((2- (piperazin-1-yl) ethyl) carbonyl) -Cmethylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone: said the compound is obtained from 3-7- [1- (4- (K ((2- (4-tertbutoxycarbonylpiperazin-1-yl) ethyl) carbonyl) -Cmethylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone ,

K-value: 0.4 (silica gel, methylene chloride / methanol / ammonia in the ratio 5: 1: 0.01), ^C 31 ^Η 33 ^N 5 ^O 4 ^, mass spectrum (EI): t / ζ = 540 [M + H ⁺ ];

(11) 3-Ζ- [1- (4- (Kpropylaminomethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone: this compound is obtained from 3 ^ - [1- (4- (Kpropyl-Ktret- butoxycarbonylaminomethyl) anilino) -1phenylmethylene] -6-methoxycarbonyl-2-indolinone,

Kg value: 0.35 (silica gel, methylene chloride / methanol 9: 1),

C27H27KO3, mass spectrum (UI): t / ζ = 440 [M – H ^- ];

(12) 3 -Ζ- [1 - (4 - ((K (3-aminopropyl) -Cmethylamino) methyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone: this compound is obtained from 3 ^ - [ 1- (4 - ((K (tert-butoxycarbonyl-3 aminopropyl) -Cmethylamino) methyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone,

K-value: 0.35 (silica gel, methylene chloride / methanol in the ratio 9: 1), ^C 28 ^Η 30 ^N 4 ^O 3 ^, mass spectrum (EI): t / ζ = 471 [M + H ⁺ ].

Example 5. 3 ^ - [1- (4-methylaminomethylanilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone.

100 mg of 3 ^ - [1- (4- (Kbenzyl-Kmetylaminomethyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2indolinone are dissolved in 20 ml of ethanol, 0.2 ml of 1N is added. hydrochloric acid and the mixture is hydrogenated for 70 minutes at room temperature and 50 psi of hydrogen pressure. Next, the reaction solution is filtered and the filtrate is evaporated on a rotary evaporator. The residue is dried at 100 ° C. under vacuum.

Yield: 50 mg (53% of theory),

K-value: 0.3 (silica gel, methylene chloride / ethanol / ammonia in the ratio 5: 1: 0.01), ^C 26 ^Η 25 ^N 3 ^O 3 ^, mass spectrum (EI): t / ζ = 426 [M- H ^- ].

Analogously to example 5 receive the following compounds:

(1) 3 -Ζ- [1- (4-methylaminomethylanilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone: the indicated compound is obtained from 3 ^ - [1- (4- (No. benzyl-Kmethylaminomethyl) anilino) -1-phenylmethylene] -6methoxycarbonyl-2-indolinone,

K-value: 0.2 (silica gel, methylene chloride / methanol / ammonia in a ratio of 10: 1: 0.01),

C25H23KO3, mass spectrum (UI): t / ζ = 412 [M – H ^- ];

(2) 3 -Ζ- [1- (4- (K (2-methylaminoethyl) -Cmethylsulfonylamino) anilino) -1-phenylmethylene] -6methoxycarbonyl-2-indolinone: this compound is obtained from 3 ^ - [1- (4- (((2- (Kbenzyl-K methylamino) ethyl) -Cmethylsulfonylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone,

K-value: 0.3 (silica gel, methylene chloride / methanol / ammonia in the ratio 10: 1: 0.01), mass spectrum (UI): t / ζ = 519 [M-H ^- ];

(3) 3 ^ - [1- (4- (К (2-aminoethyl) -Cmethylsulfonylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone: this compound is obtained from 3--| 1- (4- (No. cyanomethyl-No. methylsulfonylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone,

C26H26KO58, mass spectrum (E80: t / ζ = 505 [M – H ^- ];

(4) 3 ^ - [1- (4- (No. (3-methylaminopropyl) -Cmethylsulfonylamino) anilino) -1-phenylmethylene] -6methoxycarbonyl-2-indolinone: this compound is obtained from 3 ^ - [1- (4- ( No. (3- (No.benzyl-K methylamino) propyl) -Cmethylsulfonylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2indolinone,

- 55 006080

K-value: 0.3 (silica gel, methylene chloride / methanol / ammonia in the ratio 5: 1: 0.01), ^C 28 ^H 30 ^N 4 ^O 5 ^8, mass spectrum (E8C: t / ζ = 533 [M- H ^- ];

(5) 3 -Ζ- [1 - (4- (no. (Piperazin-1-ylmethylcarbonyl) -Nomethylamino) anilino) -1-phenylmethylene] -6methoxycarbonyl-2-indolinone: this compound is obtained from 3 ^ - [1- (4- (No. ((4-benzylpiperazin-1yl) methylcarbonyl) -Nomethylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone,

Purpose: 0.5 (silica gel, methylene chloride / methanol in a ratio of 9: 1), ^C 30 ^H 31 ^N 5 ^O 4 ^, mass spectrum (E8C: t / ζ = 524 [M – H ^- ];

(6) 3 ^ - [1- (4- (No. (methylaminomethylcarbonyl) -Nomethylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone: this compound is obtained from 3 ^ - [1- (4 - (No. ((No.benzyl-No.methylamino) methylcarbonyl) -Nomethylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone,

K-value: 0.3 (silica gel, methylene chloride / methanol in a ratio of 9: 1), ^С 2- ^Н 26 ^N 4 ^О 4 ^, mass spectrum (Е8Ц: t / ζ = 469 [М-Н ^- ];

(7) 3 ^ - [1- (4- (No. ((2-methylaminoethyl) carbonyl) -N [-methylamino) anilino) -1-phenylmethylene] -6 methoxycarbonyl-2-indolinone: this compound is obtained from 3 ^ - [ 1- (4- (No. ((2- (No.Benzyl No. Methylamino) ethyl) carbonyl) -Nmethylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone,

K-value: 0.3 (silica gel, methylene chloride / methanol / ammonia in the ratio 5: 1: 0.01), ^C 28 ^H 28 ^N 4 ^O 4 ^, mass spectrum (E8C: t / ζ = 483 [M-H ^- ].

Example 6. 3 ^ - [1- (4-ureidomethylanilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone.

300 mg of 3 ^ - [1- (4-aminomethylanilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone are dissolved in 15 ml of methanol and 200 ml of triethylamine are added. 400 mg of potassium cyanate in 5 ml of water are then added. After stirring for 2 days at room temperature, the reaction solution is evaporated on a rotary evaporator, the residue is dissolved in methylene chloride and washed once with water and saturated sodium chloride solution. The organic phase is dried over sodium sulphate and evaporated on a rotary evaporator. The residue is dried at 100 ° C. under vacuum.

Yield: 100 mg (21% of theory),

K-value: 0.7 (silica gel, methylene chloride / methanol in the ratio 5: 1), mass spectrum (E8C: t / ζ = 441 [M-H ^- ].

Example 7. 3 ^ - [1- (4-guanidinomethylanilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone.

300 mg of 3 ^ - [1- (4-aminomethylanilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone are dissolved in 5 ml of dimethylformamide and 300 ml of triethylamine are added. After that, 700 mg of amidine 3,5-dimethylpyrazole-1-carboxylic acid in 5 ml of dimethylformamide are added. After stirring for one day at room temperature, the reaction solution is evaporated on a rotary evaporator. The residue is dried at 100 ° C. under vacuum.

Yield: 200 mg (87% of theory),

K-value: 0.1 (reversed phase KR 8, methanol / 5% solution of sodium chloride in the ratio 6: 4),

C25H23 ^ O3, mass spectrum: t / ζ = 441 [M ⁴ ].

Example 8. 3 -Ζ- [1- (4-acetylaminomethylanilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone.

100 mg of 3 ^ - [1- (4-aminomethylanilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone are dissolved in 5 ml of glacial acetic acid, 0.1 ml of acetic anhydride is added and the mixture is stirred for 10 minutes at room temperature. After that, the reaction solution is poured into a saturated solution of soda and extracted four times with methylene chloride. The combined organic phases are washed with a saturated solution of sodium chloride, dried over sodium sulfate and evaporated on a rotary evaporator. The residue is dried at 100 ° C. under vacuum.

Yield: 20 mg (23% of theory),

Cg value: 0.4 (silica gel, methylene chloride / methanol in the ratio 10: 1), ^C 26 ^H 23 ^N 3 ^O 4 ^, mass spectrum (E8C: t / ζ = 440 [M – H ^- ]).

Analogously to example 8 receive the following compounds:

(1) 3 -Ζ- [1- (4- (#methylsulfonylaminomethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2indolinone: the specified compound is obtained from 3 ^ - [1- (4-aminomethylanilino) -1-phenylmethylene ] -6methoxycarbonyl-2-indolinone and methanesulfonyl chloride / triethylamine,

K-value: 0.7 (silica gel, methylene chloride / methanol in the ratio 5: 1), ^C 25 ^H 23 ^N 3 ^O 5 ^8,

- 56 006080 mass spectrum (ES): t / ζ = 476 [M – H ^- ];

(2) 3 -Ζ- [1 - (4- (4-benzoylpiperazin-1-ylmethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2indolinone: said compound is obtained from 3 ^ - [1- (4- ( piperazin-1-ylmethyl) anilino) -1phenylmethylene] -6-methoxycarbonyl-2-indolinone and benzoyl chloride,

K-value: 0.7 (silica gel, methylene chloride / methanol = 10: 1), ^C 35 32 ^N 4 ^Η ^Ο ^4, MS (WU): m / ζ = 571 [M-H ^-];

(3) 3 -Ζ- [1 - (4 - ((Ν- (3-acetylaminopropyl) -Nomethylamino) methyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone: this compound is obtained from 3 ^ - [1- (4 - ((No. (3-aminopropyl) -N methylamino) methyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone,

K-value: 0.3 (silica gel, methylene chloride / methanol 9: 1) 30 ^C 32 ^N 4 ^Η ^Ο ^4, MS (WU): m / ζ - 511 [M-H ^-].

Example 9. 3 ^ - [1- (4- (piperidin-1-ylmethyl) anilino) -1-phenylmethylene] -6-carboxy-2-indolinone.

0.8 g of 3 -Ζ- [1- (4- (piperidin-1-ylmethyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone is dissolved in 30 ml of ethanol, 8.3 ml of 1N is added. caustic soda and the mixture is stirred for 1 h at 80 ° C. After cooling, neutralized with 8.3 ml of 1N. of hydrochloric acid. The precipitate formed is suction filtered, washed with water, ethanol and ether and dried in vacuo at 100 ° C.

Output: 0.7 g (89% of theory),

K-value: 0.2 (silica gel, methylene chloride / methanol in the ratio 5: 2),

C28K7 ^ O3, mass spectrum: t / ζ = 453 [M ⁺ ].

Analogously to example 9 receive the following compounds:

(1) 3 ^ - [1- (4-bromoanilino) -1-phenylmethylene] -6-carboxy-2-indolinone: this compound is obtained from 3 -Ζ- [1 - (4-bromoanilino) -1-phenylmethylene] - 6-ethoxycarbonyl-2-indolinone,

K-value: 0.4 (silica gel, toluene / ethyl acetate in the ratio 5: 1), ^C 22 ^Η 15 ^{V ^ N} 2 ^Ο 3 ^, mass spectrum (ES): t / ζ = 435/437 [Μ + ⁺ ];

(2) 3 -Ζ- [1 - (3 - (dimethylaminomethyl) anilino) -1-phenylmethylene] -6-carboxy-2-indolinone: the indicated compound is obtained from 3 ^ - [1- (3- (dimethylaminomethyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2indolinone,

K-value: 0.7 (reversed phase KR 8, methanol / 5% solution of sodium chloride in the ratio 4: 1),

C LAES) ;, mass spectrum (ES): t / ζ = 414 [M + H ⁺ ];

(3) 3 ^ - [1- (4- (dimethylaminomethyl) anilino) -1-phenylmethylene] -6-carboxy-2-indolinone: this compound is obtained from 3 ^ - [1- (4- (dimethylaminomethyl) anilino) - - 1-phenylmethylene] -6-ethoxycarbonyl-2indolinone,

C LAES); mass spectrum (ES): t / ζ = 412 [M – H ^- ];

(4) 3 -Ζ- [1 - (4 - [(2,6-dimethylpiperidin-1-yl) methyl] anilino) -1-phenylmethylene] -6-carboxy-2-indolinone: this compound is obtained from 3 ^ - [1- (4 - [(2,6-dimethylpiperidin-1-yl) methyl] anilino) -1phenylmethylene] -6-ethoxycarbonyl-2-indolinone,

K-value: 0.6 (reversed phase KR 8, methanol / 5% solution of sodium chloride in the ratio 4: 1), ^With cost1N3c3, mass spectrum (ES): t / ζ = 482 [M + H ⁺ ] ;

(5) 3 -Ζ- [1- (4- (1-methylimidazol-2-yl) anilino) -1-phenylmethylene] -6-carboxy-2-indolinone: this compound is obtained from 3 ^ - [1- (4 - (1-methylimidazol-2-yl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone,

K-value: 0.6 (reversed phase KR 8, methanol / 5% solution of sodium chloride in the ratio 4: 1), mass spectrum (ES): t / ζ = 435 [M – H ^- ];

(6) 3 ^ - [1- (4- (No. acetyl-No dimethylaminocarbonylmethylamino) anilino) -1-phenylmethylene] -6-carboxy-2-indolinone: this compound is obtained from 3 ^ - [1- (4- (No. acetyl number dimethylaminocarbonylmethylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone,

K-value: 0.3 (silica gel, methylene chloride / methanol in the ratio 10: 1), ^C 28 ^Η 26 ^N 4 ^Ο 5 ^, mass spectrum (ES): t / ζ = 497 [M-H ^- ];

- 57 006080 (7) 3 ^ - [1- (4-ethylaminomethylanilino) -1-phenylmethylene] -6-carboxy-2-indolinone: the indicated compound is obtained from 3 ^ - [1- (4-ethylaminomethylanilino) -1-phenylmethylene ] -6-methoxycarbonyl-2-indolinone,

I _g value: 0.6 (reversed phase YAR 8, methanol / 5% solution of sodium chloride in the ratio 4: 1), ^C 25 ^Η 23 ^N 3 ^O 3 ^, mass spectrum (Ε8 Ι): t / = 412 [MN ^- ];

(8) 3-Ζ- [1 - (4-U-dimethylaminomethylcarbonyl-N-methylamino) anilino) -1-phenylmethylene] -6-carboxy-2-indolinone: the said compound is obtained from 3 ^ - [1- (4- U-dimethylaminomethylcarbonyl-Ymethylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone,

I ^ -value: 0.6 (reversed phase of YAR 8, methanol / 5% solution of sodium chloride in the ratio 4: 1), ^C 27 ^Η 26 ^N 4 ^O 4 ^, mass spectrum (Ε8): t / = 469 [M-H ⁺ ];

(9) 3 -Ζ- [1 - (4- (L-tert-butoxycarbonylethylaminomethyl) anilino) -1-phenylmethylene] -6-carboxy-2indolinone: the compound is obtained from 3 ^ - [1- (4- (L- tert-butoxycarbonylethylaminomethyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone,

Ratio: 0.4 (silica gel, methylene chloride / methanol 10: 1),

Sz0Ηz1NzO5, mass spectrum (Ε8Ι): t / ζ = 512 [M – H ^- ];

(10) 3 -Ζ- [1- (4- (U-carboxymethyl-I-methylamino) methyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone: this compound is obtained from 3 ^ - [1- (4 - ((S-ethoxycarbonylmethyl-M-methylamino) methyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone,

I _g value: 0.4 (silica gel, methylene chloride / methanol in the ratio 6: 1), ^C 27 ^Η 25 ^N 3 ^O 5 ^, mass spectrum (Ε 8 Ι): t / ζ = 470 [M – H ^- ].

Example 10. 3 -Ζ- [1 - (4- (piperidin-1-ylmethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone.

0.9 g of 3 ^ - [1- (4- (piperidin-1-ylmethyl) anilino) -1-phenylmethylene] -6-carboxy-2-indolinone are suspended in 35 ml of dimethylformamide and 0.4 g of carbonyldiimidazole is added. The mixture is stirred for 14 hours at 80 ° C. After that, add 20 ml of methanol and stirred for 3 h at 50 ° C. Then the solvent is distilled off and the residue is purified on a silica gel column using methylene chloride / methanol (3: 1) as a solvent.

Yield: 0.5 g (49% of theory),

I _g value: 0.5 (aluminum oxide, methylene chloride / methanol in a ratio of 30: 1), ^C 29I29M3O3, mass spectrum (Ε8Ι): t / ζ = 468 [M + H ⁺ ].

Analogously to example 10 receive the following compounds:

(1) 3 -Ζ - [1- (4- (piperidin-1-methylmethyl) anilino) -1-phenylmethylene] -6-benzyloxycarbonyl-2-indolinone: this compound is obtained from 3 ^ - [1- (4- ( piperidin-1-ylmethyl) anilino) -1-phenylmethylene] 6-carboxy-2-indolinone and benzyl alcohol,

Ratio: 0.6 (alumina, methylene chloride / methanol 30: 1),

C35I33M3O3, mass spectrum: t / ζ = 543 [M ⁴ ];

(2) 3 -Ζ- [1- (4- (piperidin-1-ylmethyl) anilino) -1-phenylmethylene] -6-isopropyloxycarbonyl-2-indolinone: this compound is obtained from 3 ^ - [1- (4- ( piperidin-1-ylmethyl) anilino) -1-phenylmethylene] 6-carboxy-2-indolinone and isopropanol,

I _g value: 0.4 (aluminum oxide, methylene chloride / isopropanol in the ratio 30: 1), mass spectrum: t / ζ = 495 [M ⁺ ];

(3) 3 -Ζ- [1- (4- (piperidin-1-methylmethyl) anilino) -1-phenylmethylene] -6-propyloxycarbonyl-2-indolinone: this compound is obtained from 3 ^ - [1- (4- ( piperidin-1-ylmethyl) anilino) -1-phenylmethylene] 6-carboxy-2-indolinone and n-propanol,

Ratio: 0.7 (silica gel, methylene chloride / methanol 5: 1),

С31Щ3ЩО3, mass spectrum: t / ζ = 495 [М ⁴ ];

(4) 3 -Ζ- [1- (4- (piperidin-1-ylmethyl) anilino) -1-phenylmethylene] -6-butyloxycarbonyl-2-indolinone: this compound is obtained from 3 ^ - [1- (4- ( piperidin-1-ylmethyl) anilino) -1-phenylmethylene] -6carboxy-2-indolinone and n-butanol,

I _g value: 0.5 (silica gel, methylene chloride / methanol in the ratio 10: 1), ^C 32 ^Η 35 ^N 3 ^O 3 ^, mass spectrum: t / = 509 [M ^- ];

- 58 006080 (5) 3 ^ - [1- (4-bromoanilino) -1-phenylmethylene] -6-carbamoyl-2-indolinone: the indicated compound is obtained from 3 ^ - [1- (4-bromoanilino) -1-phenylmethylene ] -6-carboxy-2-indolinone and ammonia,

B-value: 0.5 (silica gel, methylene chloride / methanol in the ratio 10: 1), ^C 22 ^H 16 ^{Β ^ N} 2 ^O 3 ^, mass spectrum: t / ζ = 432/434 [M – H ^- ];

(6) 3 -Ζ- [1- (4- (piperidin-1 -ylmethyl) anilino) -1-phenylmethylene] -6-ethylcarbamoyl-2-indolinone: this compound is obtained from 3 ^ - [1- (4- ( piperidin-1-ylmethyl) anilino) -1-phenylmethylene] -6-carboxy2-indolinone and ethylamine gas,

B-value: 0.6 (silica gel, methylene chloride / methanol in the ratio 5: 1), ^C 30 ^Η 32 ^N 4 ^Ο 2 ^, mass spectrum: t / = 480 [M ^- ];

(7) 3 ^ - [1- (4- (dimethylaminomethyl) anilino) -1-phenylmethylene] -6 - [(2-methoxyethoxy) carbonyl] -2indolinone: this compound is obtained from 3 ^ - [1- (4- ( dimethylaminomethyl) anilino) -1-phenylmethylene] -6-carboxy-2-indolinone and methyl glycol,

B-value: 0.8 (silica gel, methylene chloride / methanol in the ratio 4: 1), ^C 25 ^Η 23 ^N 3 ^Ο 3 ^, mass spectrum (EM): t / ζ = 470 [M-H ^- ];

(8) 3 ^ - [1- (4- (dimethylaminomethyl) anilino) -1-phenylmethylene] -6 - [(2-dimethylaminoethoxy) carbonyl] -2-indolinone: this compound is obtained from 3 ^ - [1- (4 - (dimethylaminomethyl) anilino) -1-phenylmethylene] -6-carboxy-2-indolinone and 2-dimethylaminoethanol,

B-value: 0.5 (silica gel, methylene chloride / methanol 5: 2 ratio),

C29H32 ^ Oe, mass spectrum (EM): t / ζ = 483 [M – H ^- ];

(9) 3 ^ - [1- (4- (dimethylaminomethyl) anilino) -1-phenylmethylene] -6 - [(2-No. Tert-butoxycarbonylaminoethoxy) carbonyl] -2-indolinone: this compound is obtained from 3 ^ - [1 - (4- (dimethylaminomethyl) anilino) -1-phenylmethylene] -6-carboxy-2-indolinone and 2-no. T-butoxycarbonylaminoethanol,

B-value: 0.8 (silica gel, methylene chloride / methanol in the ratio 5: 2), ^C 32 ^Η 36 ^N 4 ^Ο 5 ^, mass spectrum (EM): t / ζ = 412 [M – H ^- ];

(10) 3 -Ζ- [1- (4- (dimethylaminomethyl) anilino) -1-phenylmethylene] -6 - [(2,2,2-trifluoroethoxy) carbonyl] 2-indolinone: this compound is obtained from 3 ^ - [ 1- (4- (dimethylaminomethyl) anilino) -1-phenylmethylene] -6-carboxy-2-indolinone and 2,2,2-trifluoroethanol,

B-value: 0.5 (silica gel, methylene chloride / methanol in the ratio 5: 1),

C27H24? 3 ^ O3, mass spectrum (EM): t / ζ = 494 [M – H ^- ].

Example 11. 3 ^ - [1- (4- (piperidin-1-ylmethyl) anilino) -1-phenylmethylene] -6-carbamoyl-2-indolinone.

0.9 g of 3 ^ - [1- (4- (piperidin-1-ylmethyl) anilino) -1-phenylmethylene] -6-carboxy-2-indolinone, 0.8 g of TBTU and 0.4 g of the HOBT are suspended in 25 ml of dimethylformamide and add 1.0 ml of triethylamine. The mixture is stirred for 15 minutes at room temperature. After that, at 10-15 ° C for 15 minutes, it was bubbled with ammonia gas and stirred for 1.5 hours at room temperature. The precipitate formed is suction filtered, washed with water, ethanol and ether and dried in vacuo at 100 ° C.

Output: 0.6 g (64% of theory),

B value: 0.4 (BP 8 reverse phase, methanol / 5% saline solution = 6: 4), ^C 28 28 ^N 4 ^Η ^Ο ^2, MS (EM): m / ζ = 453 [M + H ⁺ ].

Analogously to example 11, the following compounds are obtained:

(1) 3 -Ζ- [1- (4- (piperidin-1-methylmethyl) anilino) -1-phenylmethylene] -6-dimethylcarbamoyl-2-indolinone: this compound is obtained from 3-2- [1- (4- (piperidin-1-ylmethyl) anilino) -1-phenylmethylene] -6carboxy-2-indolinone and dimethylamine hydrochloride / diisopropylethylamine,

B-value: 0.5 (silica gel, methylene chloride / methanol in the ratio 5: 1), ^C 30 ^Η 32 ^N 4 ^Ο 2 ^, mass spectrum (EM): t / ζ = 481 [M + H ⁺ ];

(2) 3 -Ζ - [1- (4- (piperidin-1-ylmethyl) anilino) -1-phenylmethylene] -6- (#ethyl-No.methylcarbamoyl) -2 -indolinone: this compound is obtained from 3 ^ - [1- (4- (piperidin-1-ylmethyl) anilino) -1-phenylmethylene] -6-carboxy-2-indolinone and No. ethyl-No. methylamine,

B-value: 0.5 (aluminum oxide, methylene chloride / ethanol in a ratio of 20: 1), ^C 31 ^Η 34 ^N 4 ^Ο 2 ^, mass spectrum (EM): t / ζ = 495 [M + H ⁺ ];

- 59 006080 (3) 3 ^ - [1- (4- (piperidin-1-ylmethyl) anilino) -1-phenylmethylene] -6-methylcarbamoyl-2-indolinone: this compound is obtained from 3 ^ - [1- (4 - (piperidin-1-ylmethyl) anilino) -1-phenylmethylene] -6carboxy-2-indolinone and methylamine hydrochloride / diisopropylethylamine,

K-value: 0.3 (aluminum oxide, methylene chloride / ethanol in a ratio of 20: 1), ^C 29 ^H 30 ^N 4 ^O 2 ^, mass spectrum (E8C: t / ζ = 467 [M + H ⁺ ]);

(4) 3 ^ - [1- (3- (dimethylaminomethyl) anilino) -1-phenylmethylene] -6-methylcarbamoyl-2-indolinone: this compound is obtained from 3 ^ - [1- (3- (dimethylaminomethyl) anilino) - 1-phenylmethylene] -6-carboxy-2indolinone and methylamine hydrochloride / triethylamine,

K-value: 0.3 (silica gel, methylene chloride / ethanol in the ratio 2: 1), ^C 26 ^H 26 ^N 4 ^O 2 ^, mass spectrum: t / ζ = 426 [M ⁺ ];

(5) 3 -Ζ- [1- (4- (piperidin-1-ylmethyl) anilino) -1-phenylmethylene] -6- (2-hydroxyethylcarbamoyl) -2 -indolinone: this compound is obtained from 3 ^ - [1- (4 - (piperidin-1-ylmethyl) anilino) -1-phenylmethylene] -6-carboxy-2-indolinone and ethanolamine / diisopropylethylamine,

K-value: 0.5 (aluminum oxide, methylene chloride / methanol in a ratio of 20: 1), ^C 30 ^H 32 ^N 4 ^O 3 ^, mass spectrum (E 8 C: t / ζ = 495 [M – H ^- ];

(6) 3 -Ζ- [1- (4- (piperidin-1-methylmethyl) anilino) -1-phenylmethylene] -6-diethylcarbamoyl-2-indolinone: this compound is obtained from 3 ^ - [1- (4- ( piperidin-1-ylmethyl) anilino) -1-phenylmethylene] -6carboxy-2-indolinone and diethylamine hydrochloride / diisopropylethylamine,

K-value: 0.8 (aluminum oxide, methylene chloride / methanol in a ratio of 10: 1), ^C 32 ^H 36 ^N 4 ^O 2 ^, mass spectrum (E8C: t / ζ = 509 [M + H ⁺ ]);

(7) 3 -Ζ- [1- (4- (No. tert-butoxycarbonylethylaminomethyl) anilino) -1-phenylmethylene] -6-carbamoyl-2indolinone: this compound is obtained from 3 ^ - [1- (4- (No. tert butoxycarbonylethylaminomethyl) anilino) -1-phenylmethylene] -6-carboxy-2-indolinone,

K-value: 0.3 (silica gel, toluene / ethyl acetate / ethanol in the ratio 4: 2: 1), ^C 30 ^H 32 ^N 4 ^O 4 ^, mass spectrum (E8C: t / ζ = 511 [M – H ^- ] ;

(8) 3 ^ - [1- (4- (No. dimethylaminomethylcarbonyl-No.methylamino) anilino) -1-phenylmethylene] -6-carbamoyl-2-indolinone: this compound is obtained from 3 ^ - [1- (4- (No. dimethylaminomethylcarbonyl-No. methylamino) anilino) -1-phenylmethylene] -6-carboxy-2-indolinone,

K-value: 0.5 (silica gel, methylene chloride / methanol / ammonia in the ratio 5: 1: 0.01), ^С 27Н27 ^ Oz, mass spectrum (Е8Ц: t / ζ = 468 [М-Н ^- ].

Example 12. 3 ^ - [1- (4- (No. dimethylaminomethylcarbonyl-No.methylamino) anilino) -1-phenylmethylene] -6methoxycarbonyl-2-indolinone x citric acid.

3.25 g of citric acid monohydrate are placed in 50 ml of methanol and 5.0 g of 3 ^ - [1- (4- (dimethylaminomethylcarbonyl-nmethylamino) anilino) -1-phenylmethylene] -6methoxycarbonyl-2-indolinone are added at room temperature . The solution obtained is concentrated, the residue is washed with ether and recrystallized from ethyl acetate.

Yield: 6.3 g (90% of theory),

K-value: 0.6 (silica gel, methylene chloride / methanol / ammonia in a ratio of 5: 1: 0.01),

K: 198 ° C, ^C 28 ^H 28 ^N 4 ^O 5 X ^C 6 ^H 8 ^O 7 ^, mass spectrum (E8C: t / ζ = 483 [M – H ^- ], elemental analysis: calc .: C 60.34 H 5.37 N 8.28 detectable: C 59.98 H 5.25 N 8.13

Analogously to example 12, the following compound is obtained:

(1) 3 -Ζ- [1- (4- (dimethylaminomethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone x methanesulfonic acid: the specified compound is obtained from 3 ^ - [1- (4- (dimethylaminomethyl ) anilino) 1-phenylmethylene] -6-methoxycarbonyl-2-indolinone and methanesulfonic acid,

V 275 ° C

C26H25 ^ Oz X CH4O38, mass spectrum (E8C: t / ζ = 426 [M-H ^- ], elemental analysis: calc .: C 61.92 H 5.59 N 8.03 8 6.12 detect. C 61.43 H 5.87 N 7.85 8 5.39

Similar to the examples described above, the following compounds can be obtained:

(1) 3-Ζ- (1-anilino-1-phenylmethylene) -6-ethoxycarbonyl-2-indolinone,

- 60 006080 (2) 3-Ζ- [1 - (4-nitroanilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (3) 3-Ζ- [1 - (4-fluoroanilino) -1 - phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (4) 3-Ζ- [1 - (4-chloroanilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (5) 3-Ζ- [1 - (4-iodoanilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (6) 3-Ζ- [1 - (4-cyanoanilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (7 ) 3-Ζ- [1 - (4-methoxyanilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (8) 3--[1 - (4-ethoxyanilino) -1-phenylmethylene] -6- ethoxycarbonyl-2-indolinone, (9) 3-Ζ- [1 - (4-trifluoromethylanilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indo INON, (10) 3-Ζ- [1 - (4-methylanilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (11) 3-Ζ- [1 - (4-methylmercaptoanilino) -1-phenylmethylene ] -6-ethoxycarbonyl-2-indolinone, (12) 3-Ζ- [1 - (4-aminomethylanilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (13) 3-Ζ- [1 - ( 4- (isopropylaminomethyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (14) 3-Ζ- [1 - (4- (anilinomethyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2 β-indolinone, (15) 3-Ζ- [1 - (4- (propylaminomethyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (16) 3 ^ - [1- (4- (butylaminomethyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, ( 17) 3-Ζ- [1 - (4- (isobutylaminomethyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (18) 3-Ζ- [1 - (4- (cyclohexylaminomethyl) anilino) - 1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (19) 3-Ζ- [1 - (4- (benzylaminomethyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (20) 3 - Ζ- [1 - (4 - ((No. ethyl-Methyl-amino) methyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (21) 3 ^ - [1- (4 - ((C- methyl-no. propylamino) methyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2indolinone, (22) 3 -Ζ- [1 - (4 - ((no. Isopropyl-no. methylamino) methyl) anilino) -1-phenylmethylene ] -6-ethoxycarbonyl-2indolinone, (23) 3 ^ - [1- (4 - ((C-ethyl-No. Prop Lamino) methyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2indolinone, (24) 3 -Ζ- [1 - (4 - ((Ethyl-No. Isopropylamino) methyl) anilino) -1-phenylmethylene] -6 -ethoxycarbonyl-2 indolinone, (25) 3-Ζ- [1 - (4- (dipropylaminomethyl) anilino) -1 -phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (26) 3 ^ - [1- (4- ( Diisopropylaminomethyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (27) 3 ^ - [1- (4 - ((C-benzyl-No. ethylamino) methyl) anilino) -1-phenylmethylene] -6 -ethoxycarbonyl-2 indolinone, (28) 3-Ζ- [1 - (4- (dibenzylaminomethyl) anilino) -1 -phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (29) 3-Ζ- [1 - (4- (3,6-dihydro-2Η-pyridin-1-ylmethyl) aniline o) -1-phenylmethylene] -6-ethoxycarbonyl-2indolinone, (30) 3 -Ζ- [1 - (4- (3,5-dimethylpiperidin-1-ylmethyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl- 2 indolinone, (31) 3-Ζ- [1 - (4- (azepan-1-methylmethyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (32) 3-Ζ- [1 - (4 - (piperazin-1 -ylmethyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (33) 3-Ζ- [1 - (4- (morpholin-4-ylmethyl) anilino) -1-phenylmethylene ] -6-ethoxycarbonyl-2-indolinone, (34) 3-Ζ- [1 - (4- (thiomorpholin-4-ylmethyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (35) 3 ^ - [1- (4- (1-oxothiomorpholin-4-ylmethyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2i ndolinon, (36) 3 -Ζ- [1 - (4- (1,1-dioxothiomorpholin-4-ylmethyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2indolinone, (37) 3 ^ - [1- ( 4- (acetylaminomethyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (3 8) 3-Ζ- [1 - (4- (2-aminoethyl) anilino) -1-phenylmethylene] -6- ethoxycarbonyl-2-indolinone, (3 9) 3-Ζ- [1 - (4- (2-methylaminoethyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (40) 3-Ζ- [1 - (4- (2-ethylaminoethyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (41) 3-Ζ- [1 - (4- (2-diethylaminoethyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (42) 3-Ζ- [1 - (4- (2-piperidine-1-ylethyl) anilino) -1-phenyl Tylen] -6-ethoxycarbonyl-2-indolinone, (43) 3-Ζ- [1 - (4- (2-acetylaminoethyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (44) 3- Ζ- [1 - (4- (3-aminopropyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (45) 3--[1 - (4- (3-dimethylaminopropyl) anilino) - 1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (46) 3 ^ - [1- (4- (No. aminomethylcarbonyl-No.methylamino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (47 ) 3 -Ζ- [1 - (4- (No.methylaminomethylcarbonyl-No.methylamino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (48) 3 -Ζ- [1- (4- (No. ethylaminomethylcarbonyl -№ methylamino) anilino) -1-phenylm Thielen] -6-ethoxycarbonyl-2-indolinone,

- 61 006080 (49) 3 -Ζ- [1 - (4- (No. diethylaminomethylcarbonyl-No.methylamino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (50) 3 -Ζ- [1 - ( 4- (no. (Piperidin-1-ylmethylcarbonyl) -№methylamino) anilino) -1-phenylmethylene] -6 ethoxycarbonyl-2-indolinone, (51) 3 ^ - [1- (4- (no. (Morpholin-4-ylmethylcarbonyl)) - No. methylamino) anilino) -1-phenylmethylene] -6 ethoxycarbonyl-2-indolinone, (52) 3 -Ζ- [1 - (4- (no. (Piperazin-1-ylmethylcarbonyl) -№ methylamino) anilino) -1-phenylmethylene ] -6 ethoxycarbonyl-2-indolinone, (53) 3 -Ζ- [1 - (4- (No. (2-aminoethylcarbonyl) -Nmethylamino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (54 ) 3 -Ζ- [1 - (4- (No. (2nd tylaminoethylcarbonyl) -№methylamino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (55) 3 ^ - [1- (4- (No. (2-diethylaminoethylcarbonyl) -№methylamino) anilino) -1- phenylmethylene] -6 ethoxycarbonyl-2-indolinone, (56) 3 ^ - [1- (4- (No. acetyl-№ (2-aminoethyl) amino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2indolinone, (57) 3 ^ - [1- (4- (No. acetyl-No (2-methylaminoethyl) amino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (58) 3 -Ζ- [1- (4- (No. acetyl-No (2-methylaminopropyl) amino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (59) 3 -Ζ- [1 - (4- (No. acetyl-No. (2-piperidine -1-ylethyl) amino) anilino) -1-phenylmethyl en] -6-ethoxycarbonyl-2-indolinone, (60) 3 ^ - [1- (4- (No. acetyl-No (aminocarbonylmethyl) amino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, ( 61) 3 -2- [1 - (4- (No. acetyl-No (dimethylaminocarbonylmethyl) amino) anilino) -1-phenylmethylene] -6 ethoxycarbonyl-2-indolinone, (62) 3 -Ζ- [1- (4- ( No. acetyl-No (piperidin-1-ylcarbonylmethyl) amino) anilino) -1-phenylmethylene] -6 ethoxycarbonyl-2-indolinone, (63) 3 ^ - [1- (4- (No. methyl No. (aminocarbonyl) amino) anilino ) -1-phenylmethylene] -6-ethoxycarbonyl-2indolinone, (64) 3-Ζ- [1 - (4- (No.methyl No. (methylaminocarbonyl) amino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2- indolinone, (65) 3 -Ζ- [1 - (4- (No.methyl-No (dimethylaminocarbonyl) amino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (66) 3-Ζ- [1 - (4- (No.methyl-No (piperidine -1-ylcarbonyl) amino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (67) 3 -Ζ- [1 - (4- (No. (2-aminoethyl) -Nomethylsulfonylamino) anilino) - 1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (68) 3 -Ζ- [1 - (4- (No. (2-methylaminoethyl) -Mnomethylsulfonylamino) anilino) -1-phenylmethylene] -6 ethoxycarbonyl-2-indolinone , (69) 3 -Ζ- [1 - (4- (No. (2-ethylaminoethyl) -Nomethylsulfonylamino) anilino) -1-phenylmethylene] -6 ethoxycarbonyl-2-indolinone, (70) 3 ^ - [1- (4 - (No. (2-diethylaminoethyl) -№methyl ulfonylamino) anilino) -1-phenylmethylene] -6 ethoxycarbonyl-2-indolinone, (71) 3 -Ζ- [1 - (4- (no. (2-pyrrolidin-1-ylethyl) -№methylsulfonylamino) anilino) -1-phenylmethylene ] -6 ethoxycarbonyl-2-indolinone, (72) 3 ^ - [1- (4- (No. (2-piperidin-1-ylethyl) -Nomethylsulfonylamino) anilino) -1-phenylmethylene] -6 ethoxycarbonyl-2-indolinone, ( 73) 3 ^ - [1- (4- (No. (2-piperazin-1-yleethyl) -Nomethylsulfonylamino) anilino) -1-phenylmethylene] -6 ethoxycarbonyl-2-indolinone, (74) 3 -Ζ- [1 - (4- (No. (2- (morpholin-4-yl) ethyl) -Nomethylsulfonylamino) anilino) -1-phenylmethylene] -6 ethoxycarbonyl-2-indolinone, (75) 3 -Ζ- [1- (4- (no. (aminocarbonylmethyl) -№methylsulfo Ilamino) anilino) -1-phenylmethylene] -6 ethoxycarbonyl-2-indolinone, (76) 3 -Ζ- [1 - (4- (Ν- (methylaminocarbonylmethyl) -Ν-methylsulfonylamino) anilino) -1-phenylmethylene] -6- ethoxycarbonyl-2-indolinone, (77) 3 -Ζ- [1 - (4- (No. (ethylaminocarbonylmethyl) -Nmethylsulfonylamino) anilino) -1-phenylmethylene] 6-ethoxycarbonyl-2-indolinone, (78) 3 ^ - [ 1- (4- (No. (No. (2-dimethylaminoethyl) -Nomethylamino) carbonylmethyl) -Nomethylsulphonylamino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (79) 3 -Ζ- [1 - (4- (no. (Diethylaminocarbonylmethyl) -Nomethylsulfonylamino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone,

- 62 006080 (80) 3-Ζ- [1 - (4-Shch- (pyrrolidin-1-ylcarbonylmethyl) -Nomethylsulfonylamino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (81) 3 - Ζ- [1 - (4-Sch- (piperidin-1-ylcarbonylmethyl) -Mmethylsulfonylamino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (82) 3 -Ζ- [1 - (4- U- (piperazin-1-ylcarbonylmethyl) -Nomethylsulfonylamino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (83) 3 -Ζ- [1 - (4- (C - ((morpholine-4 -yl) carbonylmethyl) -№methylsulfonylamino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (84) 3-Ζ- [1 - (4- (2-dimethylaminoethoxy) anilino) -1-phenylmethylene] -6-ethoxycarbo yl-2-indolinone, (85) 3 ^ - [1- (4- (3-dimethylaminopropoxy) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (86) 3-Ζ- [1 - ( 4- (aminocarbonylmethyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (87) 3-Ζ- [1 - (4- (2-aminocarbonylethyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl -2-Indolinone, (88) 3-Ζ- [1 - (4- (pyridin-2-yl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (89) 3-Ζ- [1 - (4- (pyridin-3-yl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (90) 3-Ζ- [1 - (4- (pyridin-4-yl) anilino) - 1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (91) 3-Ζ- [1 - (4-U-acetyl-Nometilamino) anilino) -1-phenylmethylene ] -6-ethoxycarbonyl-2-indolinone, (92) 3 ^ - [1- (4-U-ethylcarbonyl-No. (dimethylaminocarbonylmethyl) amino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (93 ) 3-Ζ- [1 - (carbamoylmethylanilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (94) 3-Ζ- [1- (4-dimethylcarbamoylmethylanilino) -1-phenylmethylene] -6-ethoxycarbonyl- 2-indolinone, (95) 3-Ζ- [1 - (4- (piperidin-1-methylmethyl) anilino) methylene] -6-ethoxycarbonyl-2-indolinone, (96) 3-Ζ- [1 - (4- (piperidin-1-methylmethyl) anilino) propylidene] -6-ethoxycarbonyl-2-indolinone, (97) 3-Ζ- [1 - (4- (piperidin-1 -ylmethyl) anilino) butylidene] -6-ethoxycarbonyl-2 -indolinon, (98) 3 -Ζ- [1 - (4- (Ν- (3-dimethylaminopropyl) -Noacetylamino) anilino) methylene] -6-ethoxycarbonyl-2indolinone, (99) 3 -Ζ- [1 - (4- (Ν- (3 -dimethylaminopropyl) -Naacetylamino ) anilino) ethylidene] -6-ethoxycarbonyl-2indolinone, (100) 3 ^ - [1- (4-Shch- (3-dimethylaminopropyl) -X-acetylamino) anilino) propylidene] -6-ethoxycarbonyl-2-indolinone, ( 101) 3 ^ - [1- (4-Shch- (3-dimethylaminopropyl) -X-acetylamino) anilino) butylidene] -6-ethoxycarbonyl-2-indolinone, (102) 3 ^ - [1- (4-Shch- (2-dimethylaminoethyl) -X-methylsulfonylamino) anilino) methylene] -6-ethoxycarbonyl-2-indolinone, (103) 3 ^ - [1- (4- (C- (2-dimethylaminoethyl) -X-methylsulfonylamino) anilino) propyliden] -6- ethoxycarbonyl-2-indolinone, (104) 3 -Ζ- [1 - (4- (C- (2-dimethylaminoethyl) X-methylsulfonylamino) anilino) butylidene] -6-ethoxycarbonyl-2-indolinone, (105) 3 - Ζ- [1 - (4-tetrazol-5-ylanilino) methylene] -6-ethoxycarbonyl-2-indolinone, (106) 3--[1 - (4-tetrazole-5 -ilanilino) ethylidene] -6-ethoxycarbonyl -2-Indolinone, (107) 3-Ζ- [1 - (4-tetrazol-5 -ilanilino) propylidene] -6-ethoxycarbonyl-2-indolinone, (108) 3-Ζ- [1 - (4-tetrazole- 5 -ilanilino) butylidene] -6-ethoxycarbonyl-2-indolinone, (109) 3 -Ζ- [1 - (4-carboxyanilino) methylene] -6-ethoxycarbonyl-2-indolinone, (110) 3-Ζ- [1 - (4-carboxyanilino) propylidene] -6-ethoxycarbonyl-2-indolinone, (111) 3 ^ - [1- (4-carboxyanilino) butylidene] -6-ethoxycarbonyl-2-indolinone, (112) 3 ^ - [1- (4-Sch- (3-dimethylaminopropion) -X-dimethylaminocarbonylmethylamino) anilino ) -1phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (113) 3 -Ζ- [1 - (4-Sch- (4-dimethylaminobutyryl) -X-dimethylaminocarbonylmethylamino) anilino) -1phenylmethylene] -6-ethoxycarbonyl-2- indolinone, (114) 3 ^ - [1- (4-U-dimethylaminocarbonylmethyl-X- (2-dimethylaminoethylsulfonyl) amino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (115) 3 ^ - [ 1- (4-U-dimethylaminocarbonylmethyl-X- (3-dimethylaminopropylsulfonyl) amino) anilino) -1-phenylmethylene] -6-et hydroxycarbonyl-2-indolinone, (116) 3 -Ζ- [1 - (4 - ((2-hydroxyethyl) aminomethyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2indolinone, (117) 3 -Ζ- [1 - (4 - ((2-methoxyethyl) aminomethyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2indolinone, (118) 3 -Ζ- [1 - (4 - (((2-dimethylaminoethyl) aminomethyl) anilino)) - 1-phenylmethylene] -6-ethoxycarbonyl-2indolinone, (119) 3-2- [1 - (4 - ((3-dimethylaminopropyl) aminomethyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl2-indolinone, (120) 3 ^ - [1- (4- (U-tert-butoxycarbonyl-2-aminoethyl) aminomethyl) anilino) -1-phenylmethylene] -6 ethoxycarbonyl-2-indolinone,

- 63 006080 (121) 3-Ζ- [1 - (4 - ((No. tert-butoxycarbonyl-3-aminopropyl) aminomethyl) anilino) -1-phenylmethylene] 6-ethoxycarbonyl-2-indolinone, (122) 3 ^ - [1- (4 - ((2-aminoethyl) aminomethyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (123) 3 -Ζ- [1- (4 - ((3-aminopropyl) aminomethyl ) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2indolinone, (124) 3 -Ζ- [1 - (4 - ((2-acetylaminoethyl) aminomethyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2indolinone, (125) 3-Ζ- [1- (4 - ((3-acetylaminopropyl) aminomethyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl2-indolinone, (126) 3 -Ζ- [1 - (4 - (( 2-methylsulfonylaminoethyl) aminomethyl) anilino) -1 -fe Nilmethylene] -6-ethoxycarbonyl-2-indolinone, (127) 3 -Ζ- [1- (4 - ((3-methylsulfonylaminopropyl) aminomethyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (128 ) 3-Ζ- [1 - (4- (L- (L-tert-butoxycarbonyl-2-am inoethyl) -Ν-methylaminomethyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (129) 3-Ζ- [1 - (4- (H- (2-aminoethyl) -Nomethylaminomethyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (130) 3 -Ζ- [1- (4 - (No. (2-acetylaminoethyl) -Nomethylaminomethyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (131) 3-Ζ- [1 - (4- (No. (2-methylsulfonylaminoethyl) -N methylaminomethyl) anilino) -1-phenylmethyl flax] 6-ethoxycarbonyl-2-indolinone, (132) 3-Ζ- [1 - (4- (carboxymethylaminomethyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (133) 3--[ 1- (4- (ethoxycarbonylmethylaminomethyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2indolinone, (134) 3 -Ζ- [1- (4- (carbamoylmethylaminomethyl) anilino) -1 -phenylmethylene] -6-ethoxycarbonyl- 2-indolinone, (135) 3-Ζ- [1 - (4- (dimethylcarbamoylmethylaminomethyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl2-indolinone, (136) 3-Ζ- [1 - (4- (methylcarbamoylmethylaminomethyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2indolinone, (137) 3 -Ζ- [1- (4- (#dimethylaminomethylcarbonyl-№me Tylamino) -3-amino-anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (138) 3 -Ζ- [1- (4- (No. dimethylaminomethylcarbonyl-No.methylamino) -3-nitroanilino) -1-phenylmethylene ] -6-ethoxycarbonyl-2-indolinone, (139) 3-Ζ- [1 - (4- (No. dimethylaminomethylcarbonyl-No. methylamino) -3-acetylaminoanilino) -1phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (140) 3 -Ζ- [1 - (4- (No. dimethylaminomethylcarbonyl-No.methylamino) -3-methylsulfonylaminoanilino) 1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (141) 3-Ζ- [1 - (4- (no. dimethylaminomethylcarbonyl-No.methylamino) -3-cyanoanilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolino n, (142) 3 ^ - [1- (4- (No. dimethylaminomethylcarbonyl-No.methylamino) -3-hydroxyanilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (143) 3-Ζ- [1 - (4- (No. dimethylaminomethylcarbonyl-No. methylamino) -3-methoxyanilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (144) 3-Ζ- [1 - (4- (No. of dimethylaminomethylcarbonyl-No. methylamino) - 3-ethoxycarbonylanilino) -1phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (145) 3-Ζ- [1 - (4- (No. dimethylaminomethylcarbonyl-No.methylamino) -3 -carboxyanilino) -1-phenylmethylene] -6-ethoxycarbonyl -2-indolinone, (146) 3 ^ - [1- (4- (No.dimethylaminomethylcarbonyl-No.methylamino) -3-carbamoylanilino) -1- Enylmethylene] -6-ethoxycarbonyl-2-indolinone, (147) 3 -Ζ- [1- (4- (No. of dimethylaminomethylcarbonyl-No.methylamino) -3-chloroanilino) -1-phenylmethylene] 6-ethoxycarbonyl-2-indolinone, ( 148) 3 -Ζ- [1 - (4- (No. dimethylaminomethylcarbonyl-No.methylamino) -3-fluoroanilino) -1-phenylmethylene] -

6-ethoxycarbonyl-2-indolinone, (149) 3 ^ - [1- (4- (No. of dimethylaminomethylcarbonyl-No.methylamino) -3-bromoanilino) -1-phenylmethylene] 6-ethoxycarbonyl-2-indolinone, (150) 3- Ζ- [1- (4- (No. dimethylaminomethylcarbonyl-No.methylamino) -3-methylanilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (151) 3 ^ - [1- (4- (No. of dimethylaminomethylcarbonyl- No. methylamino) -3-trifluoromethylanilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone,

- 64 006080 (152) 3 ^ - [1- (4-U-dimethylaminomethylcarbonyl-No.methylamino) -3,5-dibromanilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (153) 3 ^ - [ 1- (4-Sh-dimethylaminomethylcarbonyl-No.methylamino) -3,5-dichloroanilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (154) 3 -Ζ- [1 - (4- (dimethylaminomethyl) - 3-amino-anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2indolinone, (155) 3 -Ζ- [1 - (4- (dimethylaminomethyl) -3 -nitroanilino) -1-phenylmethylene] -6-ethoxycarbonyl-2indolinone, ( 156) 3 -Ζ- [1- (4- (dimethylaminomethyl) -3-acetylaminoanilino) -1-phenylmethylene] -6-ethoxycarbonyl2-indolinone, (157) 3 -Ζ- [1- (4- (dimethylaminomethyl) -3 - ( Ethylsulfonylamino) anilino) -1-phenylmethylene] -6 ethoxycarbonyl-2-indolinone, (158) 3 -Ζ- [1 - (4- (dimethylaminomethyl) -3-cyanoanilino) -1-phenylmethylene] -6-ethoxycarbonyl-2indolinone, ( 159) 3 -Ζ- [1- (4- (dimethylaminomethyl) -3-hydroxyanilino) -1-phenylmethylene] -6-ethoxycarbonyl-2indolinone, (160) 3 -Ζ- [1- (4- (dimethylaminomethyl) -3 -methoxyanilino) -1-phenylmethylene] -6-ethoxycarbonyl-2indolinone, (161) 3 -Ζ- [1 - (4- (dimethylaminomethyl) -3 - (ethoxycarbonyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2 α-indolinone, (162) 3 -Ζ - [1 - (4- (dimethylaminomethyl) -3 -carboxyanilino) -1-phenylmethylene] -6-ethoxycarbonyl-2indolino , (163) 3 ^ - [1- (4- (dimethylaminomethyl) -3-carbamoylanilino) -1-phenylmethylene] -6-ethoxycarbonyl-2indolinone, (164) 3 -Ζ- [1- (4- (dimethylaminomethyl) - 3-chloroanilino) -1-phenylmethylene] -6-ethoxycarbonyl-2indolinone, (165) 3 -Ζ- [1- (4- (dimethylaminomethyl) -3-fluoroanilino) -1-phenylmethylene] -6-ethoxycarbonyl-2indolinone, ( 166) 3 -Ζ- [1- (4- (dimethylaminomethyl) -3-bromoanilino) -1-phenylmethylene] -6-ethoxycarbonyl-2indolinone, (167) 3 -Ζ- [1- (4- (dimethylaminomethyl) -3 -methylanilino) -1-phenylmethylene] -6-ethoxycarbonyl-2indolinone, (168) 3 -Ζ- [1 - (4- (dimethylaminomethyl) -3-trifluoromethylanilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indole non, (169) 3 ^ - [1- (4- (dimethylaminomethyl) -3,5-dibromanilino) -1-phenylmethylene] -6-ethoxycarbonyl-2indolinone, (170) 3 -Ζ- [1 - (4- ( dimethylaminomethyl) -3,5-dichloroanilino) -1-phenylmethylene] -6-ethoxycarbonyl-2indolinone, (171) 3 ^ - [1- (4-O - ((4-methylpiperazin-1-yl) methylcarbonyl) -Nmethylamino ) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (172) 3 -Ζ- [1 - (4- (Ν (imidazo-1-ylmethylcarbonyl) -Ν-methylamino) anilino) -1- phenylmethylene] -6 ethoxycarbonyl-2-indolinone, (173) 3 ^ - [1- (4- (C- (phthalimido-2-ylmethylcarbonyl) -Mmethylamino) anilino) -1-phenylmethylene] -6 ethoxycarbonyl-2-indolinone, ( 174) 3 ^ - [1- (4-O-aminomethylcarbonyl-M Etilamino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (175) 3 -Ζ - [1 - (4- (K-acetylaminomethylcarbonyl-Nmethylamino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl -2-Indolinone, (176) 3 ^ - [1- (4-U-methylsulfonylaminomethylcarbonyl-No.methylamino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (177) 3 -Ζ- [1 - (4- (C- (Sh- (2-methoxyethyl) -Nomethylamino) methylcarbonyl) -Nmethylamino) anilino) -1 phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (178) 3 ^ - [1- (4 -CH- (UH- (2-dimethylaminoethyl) -Nomethylamino) methylcarbonyl) -Nomethylamino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (179) 3 -Ζ- [1 - (4- (C- ((di- (2-hydroxyethyl) amino) methylcarbonyl) -Methylamino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (180) 3 -Ζ- [1- (4- (C-dimethylaminomethylcarbonyl - No. methylamino) anilino) methylene] -6-ethoxycarbonyl-2-indolinone, (181) 3 -Ζ- [1 - (4-Sh-dimethylaminomethylcarbonyl-No.methylamino) anilino) ethylidene] -6-ethoxycarbonyl-2-indolinone, (182) 3 -Ζ- [1 - (4-Sh-dimethylaminomethylcarbonyl-No.methylamino) anilino) propylidene] -6-ethoxycarbonyl-2-indolinone,

- 65 006080 (183) 3 ^ - [1- (4- (№ dimethylaminomethylcarbonyl-N-methylamino) anilino) butylidene] -6-ethoxycarbonyl-2-indolinone, (184) 3 ^ - [1- (4- (dimethylaminomethyl ) anilino) methylene] -6-ethoxycarbonyl-2-indolinone, (185) 3 ^ - [1- (4- (dimethylaminomethyl) anilino) ethylidene] -6-ethoxycarbonyl-2-indolinone, (186) 3 ^ - [1 - (4- (dimethylaminomethyl) anilino) propylidene] -6-ethoxycarbonyl-2-indolinone, (187) 3 -Ζ- [1 - (4- (dimethylaminomethyl) anilino) butylidene] -6-ethoxycarbonyl-2-indolinone, (( 188) 3 -Ζ - [1 - (4- (No. dimethylaminocarbonylmethylamino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (189) 3 -Ζ- [1 - (4- (Ν- (3 -dimethylaminopropyl) - N-acetylamino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (190) 3 -Ζ- [1 - (4 - ((imidazolidin-2,4-dione-5-ylidene) methyl) anilino ) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (191) 3 -Ζ- [1 - (4- (No. ((2-dimethylaminoethyl) carbonyl) -Y-methylamino) anilino) -1-phenylmethylene] -6 ethoxycarbonyl-2-indolinone, (192) 3 -Ζ- [1 - (4- (No. tert-butoxycarbonylaminomethyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl2-indolinone, (193) 3 -Ζ- [1 - (4- (2-oxopyrrolidin-1-ylmethyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2indolinone, (194) 3 -Ζ- [1- (4- (N-aminocarbonylmethyl-N-methylsulfonylamino) anilino) -1-phenylmethylene] - 6 ethoxycarbonyl-2-indolinone, (195) 3 -Ζ - [1 - (4- (No. cyanomethyl-N-methylsulfonylamino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (196) 3 -Ζ- [1 - (4- (2- (imidazol-4-yl) ethyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (197) 3-Ζ- [1- (4 - ((2 - (Ν-benzyl-Y-methylamino) ethyl) -Y-methylsulfonylamino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (198) 3 -Ζ- [1 - (4-cyclohexylaminoanilino) -1 -phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (199) 3 -Ζ- [1 - (4- (imidazol-1-ylmethyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (200 ) 3-Ζ- [1 - (4- (imidazol-1-ylmethyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (201) 3 -Ζ- [1 - (No. methylpiperidin-4-ylamino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (202) 3 -Ζ- [1 - (4- (imidazol-4-ylmethyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (203) 3 -Ζ- [1 - (4 - ((4-hydroxypiperidin-1-yl) methyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2indolinone, (204) 3-Ζ - [1- (4 - ((4-methoxypiperidin-1-yl) methyl) anilino) -1-phenylmethylene] -6 -ethoxycarbonyl-2indolinone, (205) 3 -Ζ- [1 - (4-benzylanilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (206) 3 -Ζ- [1- (4- (Ν- (3-trifluoroacetylaminopropyl) -Y-methylsulfonylamino) anilino) -1-phenylmethylene] -6 is Sicarbonyl-2-indolinone, (207) 3 -Ζ- [1 - (4- (4-tert-butoxycarbonylpiperazin-1-ylmethyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (208) 3 -Ζ- [1 - (4- (1-methylimidazol-2-yl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (209) 3 -Ζ- [1 - (4- (1 - methylimidazol-2-yl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (210) 3 -Ζ- [1 - (4- (No. (2-dimethylaminoethyl) -Y-methylsulfonylamino) -3- aminoanilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (211) 3 -Ζ- [1 - (4 - ((3 - (No. benzyl-N-methylamino) propyl) -Y-methylsulfonylamino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (212) 3 -Ζ- [1 - ( 4- (No. (2-dimethylaminoethyl) -Y-acetylamino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (213) 3-Ζ- [1 - (4- (No. (2-dimethylaminoethyl) -Y-butyrylamino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (214) 3 ^ - [1- (4- (No. (2-dimethylaminoethyl) -Y-isobutyrylamino) anilino) -1- phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (215) 3 -Ζ- [1 - (4- (L- (2-dimethylaminoethyl) -Y-benzoylamino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2 β-indolinone, (216) 3 ^ - [1- (4- (No. (2-dimethylaminoethyl) -Y-acetylamino) -3-aminoanilino) -1-phenylmethylene] -6 ethoxycarbonyl-2-indolinone, (217) 3 -Ζ - [1 - (4- (4-hydroxymethylpiperidin-1-ylmethyl ) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (218) 3 ^ - [1- (4- (2- (4-hydroxypiperidin-1-yl) ethyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2 indolinone, (219) 3 -Ζ- [1 - (4- (L- (2-dimethylaminoethyl) -Y-propylsulfonylamino) anilino) -1-phenylmethylene] -6 ethoxycarbonyl-2-indolinone,

- 66 006080 (220) 3 -Ζ- [1 - (4- (N- (2-dimethylaminoethyl) -H-butylsulfonylamino) anilino) -1-phenylmethylene] -6 ethoxycarbonyl-2-indolinone, (221) 3 ^ - [ 1- (4- (L- (2-dimethylaminoethyl) -H-phenylsulfonylamino) anilino) -1-phenylmethylene] -6 ethoxycarbonyl-2-indolinone, (222) 3 -Ζ- [1 - (4- (L- (2 -dimethylaminoethyl) -M-benzylsulfonylamino) anilino) -1-phenylmethylene] -6 ethoxycarbonyl-2-indolinone, (223) 3 -Ζ- [1 - (4 - ((imidazolidin-2,4-dione-5-yl) methyl) ) anilino) -1-phenylmethylene] -6-ethoxycarbonyl2-indolinone, (224) 3 ^ - [1- (4 - ((3-hydroxypyrrolidin-1-yl) methyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl2 β-indolinone, (225) 3 ^ - [1- (4- (cyclohexylilmet yl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (226) 3-Ζ- [1 - (4- (cyclohexylcarbonyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (227) 3-Ζ- [1 - (4-diethylaminomethylanilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (228) 3 -Ζ- [1 - (4- (K- (n-hexyl)) -Y-methylaminomethyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2indolinone, (229) 3 -Ζ- [1 - (4- (Y- (2-dimethylaminoethyl) -N- (furan-2-carbonyl) amino) anilino) -1-phenylmethylene] 6-ethoxycarbonyl-2-indolinone, (230) 3 ^ - [1- (4- (K- (2-dimethylaminoethyl) -H- (2-methoxybenzoyl) amino) anilino) - 1-phenylmethylene] 6-ethoxycarbonyl-2-indolinone, (231) 3 -Ζ- [1 - (4- ( - (2-dimethylaminoethyl) -Y- (pyridine-3-carbonyl) amino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (232) 3 ^ - [1- (4- (L- ( 2-dimethylaminoethyl) -H- (phenylacetyl) amino) anilino) -1-phenylmethylene] -6ethoxycarbonyl-2-indolinone, (233) 3 -Ζ- [1 - (4- (imidazol-2-yl) anilino) -1 -phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (234) 3 -Ζ- [1 - (4- (1-ethylimidazol-2-yl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (235) 3 -Ζ- [1 - (4- (1 -benzylimidazol-2-yl) anilino) -1-fenshetylene] -6-ethoxycarbonyl-2-indolinone, (236) 3 ^ - [1- (4- (M- (2-dimethylaminoethyl) -H-isopropylsulfonylamino) anilino) -1-phenylmethylene] 6-ethoxycarbo yl-2-indolinone, (237) 3 -Ζ- [1 - (4- (K - ((4-benzylpiperazin-1-yl) methylcarbonyl) -Y-methylamino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl -2-Indolinone, (238) 3 -Ζ- [1 - (4- (L- (pyrrolidin-1-ylmethylcarbonyl) -M-methylamino) anilino) -1-phenylmethylene] -6 ethoxycarbonyl-2-indolinone, (239) 3 -Ζ - [1- (4- (L- (2-dimethylaminoethyl) -H-acetylamino) -3-bromoanilino) -1-phenylmethylene] -6 ethoxycarbonyl-2-indolinone, (240) 3 ^ - [1- ( 4- (5-methylimidazol-4-yl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (241) 3 -Ζ- [1 - (4- (Y - ((2-dimethylaminoethyl) carbonyl ) -M-isopropylamino) anilino) -1-phenylmethylene] 6-ethoxycarbonyl-2-indolinone, (242 ) 3 ^ - [1- (4- (M - ((2-dimethylaminoethyl) carbonyl) -H-benzylamino) anilino) -1-phenylmethylene] -6ethoxycarbonyl-2-indolinone, (243) 3 -Ζ- [1 - (4- (N-butyl-M-tert-butoxycarbonylaminomethyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (244) 3 ^ - [1- (4- (M - ((M-aminocarbonylmethyl -H-methylamino) methylcarbonyl) -H-methylamino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (245) 3 -Ζ- [1 - (4- (K - ((L-benzyl- N-methylamino) methylcarbonyl) -H-methylamino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (246) 3 -Ζ- [1 - (4- (K- (di (2-methoxyethyl) aminomethylcarbonyl) -Y-methylamino) anilino) -1-phenylmethylene] -6- ethoxycarbonyl-2-indolinone, (247) 3 ^ - [1- (4- (L - ((2- (4-tert-butoxycarbonylpiperazin-1-yl) ethyl) carbonyl) -H-methylamino) anilino) -1 - phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (248) 3 -Ζ- [1 - (4- (K - ((2- (piperidin-1-yl) ethyl) carbonyl) -Y-methylamino) anilino) - 1-phenylmethylene] 6-ethoxycarbonyl-2-indolinone, (249) 3 -Ζ- [1 - (4- (L - ((2- (K-benzyl-N-methylamino) ethyl) carbonyl) -H-methylamino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (250) 3 ^ - [1- (4- (N-dimethylaminomethylcarbonyl-H-isopropylamino) anilino) -1-phenylmethylene] -6 ethoxycarbonyl-2-indolinone , (251) 3 ^ - [1- (4- (L- (piperidin-1-ylmethylcarbonyl) -H-isopro ilamino) anilino) -1-phenylmethylene] 6-ethoxycarbonyl-2-indolinone, (252) 3 -Ζ- [1 - (4- (L - ((4-tert-butoxycarbonylpiperazin-1-yl) methylcarbonyl) -M- isopropylamino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (253) 3 ^ - [1- (4- (M - ((M-benzyl-N-methylamino) methylcarbonyl) -H-benzylamino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone,

- 67 006080 (254) 3-Ζ - [1 - (4- (No. of dimethylaminomethylcarbonyl-No.Benzylamino) anilino) -1-phenylmethylene] -6 ethoxycarbonyl-2-indolinone, (255) 3 -Ζ- [1- (4- (No. (Piperidin-1-ylmethylcarbonyl) -Nbenzylamino) anilino) -1-phenylmethylene] -6 ethoxycarbonyl-2-indolinone, (256) 3 -Ζ- [1 - (4- (1,2,4-triazole-2 -ylmethyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (257) 3 -Ζ- [1 - (4- (1,2,3-triazol-2-ylmethyl) anilino) -1 - phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (258) 3 -Ζ- [1 - (4- (1,2,3-triazol-1-ylmethyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2 α-indolinone, (259) 3 -Ζ- [1 - (4 - ((α-aminocarbonylmethyl-No.methylamino) methyl) anilino) -1 -phenylmethylene] -6ethoxycarbonyl-2-indolinone, (260) 3 -Ζ- [1 - (4 - ((di- (2-methoxyethyl) amino) methyl) anilino) -1 -phenylmethylene] -6-ethoxycarbonyl-2indolinone, (261) 3 ^ - [1- (4 - ((di- (2-hydroxyethyl) amino) methyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2indolinone, (262) 3 ^ - [1- (4 - ((No. ethoxycarbonylmethyl-No.methylamino) methyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (263) 3-Ζ- [1 - (4- (azetidin-1 -ylmethyl) anilino) - 1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (264) 3 ^ - [1- (4- (No.propyl-No.t-butoxycarbonylaminomethyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (265) 3 ^ - [1- (4 - ((No. (2- (2-methoxyetho C) ethyl) -Nomethylamino) methyl) anilino) -1-phenylmethylene] -6 ethoxycarbonyl-2-indolinone, (266) 3 -Ζ- [1 - (4 - ((No. (tert-butoxycarbonyl-3-aminopropyl) - No. methylamino) methyl) anilino) -1phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (267) 3-Ζ - [1 - (4 - ((No. (methylcarbamoylmethyl) -Nomethylamino) methyl) anilino) -1-phenylmethylene ] -6 ethoxycarbonyl-2-indolinone, (268) 3 -Ζ- [1 - (4 - ((No. (dimethylcarbamoylmethyl) -Nomethylamino) methyl) anilino) -1-phenylmethylene] -6 ethoxycarbonyl-2-indolinone, (269) 3 ^ - [1- (4 - ((No. propyl-No. methylamino) methyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2indolinone, (270) 3 ^ - [1- (4 - ((No. (2 -dimethylaminoethyl) -№met lamino) methyl) anilino) -1-phenylmethylene] -6 ethoxycarbonyl-2-indolinone, (271) 3 ^ - [1- (4 - ((no. (3-dimethylaminopropyl) -Nomethylamino) methyl) anilino) -1-phenylmethylene ] -6 ethoxycarbonyl-2-indolinone, (272) 3 ^ - [1- (4 - ((no. (2-methoxyethyl) -Nmethylamino) methyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (273) 3 ^ - [1- (4 - ((no. (2-hydroxyethyl) -Nomethylamino) methyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (274) 3 -Ζ- [[ 1 - (4 - ((no. (Dioxolan-2-ylmethyl) -Nomethylamino) methyl) anilino) -1-phenylmethylene] -6 ethoxycarbonyl-2-indolinone, (275) 3 -Ζ- [1- (4- (3 -oxopiperazin-1-ylmethyl) anilino) -1-phenylmethylene] -6-ethoxycar Bonil-2indolinon, (276) 3 -Ζ- [1 - (4- (P- (piperazin-1-ylmethylcarbonyl) -N isopropylamino) anilino) -1-phenylmethylene] 6-ethoxycarbonyl-2-indolinone, (277) 3 -Ζ- [1 - (4- (No. ((2- (piperazin-1-yl) ethyl) carbonyl) -Nomethylamino) anilino) -1-phenylmethylene] -6 ethoxycarbonyl-2-indolinone, (278) 3 -Ζ - [1 - (4 - ((Ν- (3-aminopropyl) -Nomethylamino) methyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (279) 3 ^ - [1- (4- (No. (3-methylaminopropyl) -Nomethylsulfonylamino) anilino) -1-phenylmethylene] -6 ethoxycarbonyl-2-indolinone, (280) 3-Ζ- [1- (4-ureidomethylanilino) -1-phenylmethylene] -6-ethoxycarbonyl- 2-indolinone, (281) 3 ^ - [1- (4-guanidinomethyl nilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (282) 3 -Ζ- [1 - (4- (No. methylsulfonylaminomethyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2indolinone, (283) 3 ^ - [1- (4- (4-benzoylpiperazin-1-ylmethyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2indolinone, (284) 3 ^ - [1- (4 - (No. (3- acetylaminopropyl) -№ methylamino) methyl) anilino) -1-phenylmethylene] -6 ethoxycarbonyl-2-indolinone, (285) 3 -Ζ- [1 - (4 - ((Ν- (3-methylsulfonylaminopropyl) -№ methylamino) methyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone,

- 68 006080 (286) 3 -Ζ- [1 - (4 - ((N-carboxymethyl-N-methylamino) methyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone, (287) 3 ^ - (1-anilino-1-phenylmethylene) -6-methoxycarbonyl-2-indolinone, (288) 3-Ζ- [1 - (4-nitroanilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone, (289) 3 ^ - [1- (4-fluoroanilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone, (290) 3-Ζ- [1- (4-chloroanilino) -1-phenylmethylene] -6-methoxycarbonyl- 2-indolinone, (291) 3-Ζ- [1 - (4-bromoanilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone, (292) 3--[1 - (4-iodoanilino) -1 -phenylmethylene] -6-methoxycarbonyl-2-indolinone, (293) 3-Ζ- [1 - (4-cyanoanilino) -1-phenylmethylene ] -6-methoxycarbonyl-2-indolinone, (294) 3 -Ζ- [1 - (4-carboxyanilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone, (295) 3 -Ζ- [1 - ( 4-methoxyanilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone, (296) 3 -Ζ- [1 - (4-this is xianilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone, (297 ) 3 -Ζ- [1- (4-trifluoromethylanilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone, (298) 3 -Ζ- [1 - (4-methylmercate'anilino) -1-phenylmethylene] - 6-methoxycarbonyl-2-indolinone, (299) 3 -Ζ- [1 - (4- (isopropylaminomethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone, (300) 3 -Ζ- [1 - (4- (anilinomethyl) anilino) -1-phenylmethylene] -6-meth hydroxycarbonyl-2-indolinone, (301) 3-Ζ- [1 - (4- (isobutylaminomethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone, (302) 3 -Ζ- [1 - (4 - (cyclohexylaminomethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone, (303) 3 -Ζ- [1 - (4- (benzylaminomethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2- indolinone, (304) 3 ^ - [1- (4 - ((N-methyl-N-propylamino) methyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2indolinone, (305) 3 -Ζ- [1 - (4 - ((N-isopropyl-N-methylamino) methyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone, (306) 3 -2- [1 - (4 - ((M-ethyl- M-propylamino) methyl) anilino) -1-phenylmethylene] -6-methoxycar onyl-2 indolinone, (307) 3-Ζ- [1 - (4 - ((L-ethyl-H-isopropylamino) methyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl2-indolinone, (308) 3 ^ - [ 1- (4- (dipropylaminomethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone, (309) 3 -Ζ- [1- (4- (diisopropylaminomethyl) anilino) -1-phenylmethylene] -6- methoxycarbonyl-2-indolinone, (310) 3 -Ζ- [1 - (4 - ((L-benzyl-M-ethylamino) methyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2indolinone, (311) 3 ^ - [1- (4- (dibenzylaminomethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone, (312) 3 -Ζ- [1 - (4- (3,6-dihydro-2H-pyridine- 1-ylmethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-and Dolinone, (313) 3 -Ζ- [1 - (4- (3,5-dimethylpiperidin-1-ylmethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl2-indolinone, (314) 3-Ζ- [1 - (4- (azepan-1 -ylmethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone, (315) 3 -Ζ- [1 - (4- (2-aminoethyl) anilino) -1-phenylmethylene ] -6-methoxycarbonyl-2-indolinone, (316) 3-7- [1 - (4- (2-methylaminoethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone, (317) 3 -Ζ - [1 - (4- (2-ethylaminoethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone, (318) 3 -Ζ- [1 - (4- (2-dimethylaminoethyl) anilino) -1 -phenylmethylene] -6-methoxycarbonyl-2-indolinone, (319) 3 -Ζ- [1 - (4- (2-diethylaminoethyl) anilino) - 1-phenylmethylene] -6-methoxycarbonyl-2-indolinone, (320) 3 -Ζ- [1 - (4- (2-piperidine-1-ylethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone , (321) 3 -Ζ- [1- (4- (2-acetylaminoethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone, (322) 3-Ζ- [1- (4- (3 -aminopropyl) anilino) -1 -phenylmethylene] -6-methoxycarbonyl-2-indolinone, (323) 3 -Ζ- [1 - (4- (3 -dimethylaminopropyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2 α-indolinone, (324) 3 ^ - [1- (4- (M-aminomethylcarbonyl-N-methylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone, (325) 3 ^ - [1- ( 4- (N-ethylaminomethylcarbonyl-N-methylamino) anilino) -1-phenylmethyl flax] -6-methoxycarbonyl-2-indolinone, (326) 3 -Ζ- [1 - (4- (K-diethylaminomethylcarbonyl-N-methylamino) anilino) -1-phenylmethylene] -6methoxycarbonyl-2-indolinone, (327) 3 -Ζ- [1 - (4- (M-dipropylaminomethylcarbonyl-M-methylamino) anilino) -1-phenylmethylene] -6methoxycarbonyl-2-indolinone, (328) 3 ^ - [1- (4- (S - (( K-ethyl-N-methylamino) methylcarbonyl) -H-methylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone,

- 69 006080 (329) 3 -Ζ- [1 - (4-Shch- (Sh-ethyl-N-propylamino) methylcarbonyl) -H-methylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone, (330) 3 -Ζ- [1 - (4-Shch- (Sh-methyl-N-propylamino) methylcarbonyl) -H-methylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone, (331) 3 -Ζ- [1 - (4-U-dimethylaminomethylcarbonyl-N-ethylamino) anilino) -1-phenylmethylene] -6methoxycarbonyl-2-indolinone, (332) 3 -2- [1 - (4-U-Dimethylaminomethylcarbonyl-H -propylamino) anilino) -1-phenylmethylene] -6methoxycarbonyl-2-indolinone, (333) 3 -Ζ- [1 - (4-U-dimethylaminomethylcarbonyl-N-butylamino) anilino) -1-phenylmethylene] -6methoxycarbo yl-2-indolinone, (334) 3 ^ - [1- (4- (L- (2-aminoethylcarbonyl) -H-methylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone, (335) 3 ^ - [1- (4-Shch- (2-diethylaminoethylcarbonyl) -Y-methylamino) anilino) -1-phenylmethylene] -6methoxycarbonyl-2-indolinone, (336) 3-Ζ- [1- (4-Shch- acetyl-N- (2-aminoethyl) amino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2indolinone, (337) 3-Ζ- [1 - (4-Sch-acetyl-N- (2-methylaminoethyl) amino ) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone, (338) 3 -Ζ - [1 - (4-U-acetyl-I- (3-methylaminopropyl) amino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone, (339) 3 ^ - [1- (4- (L-acetyl-H- (2-piperidin-1-and latyl) amino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone, (340) 3 ^ - [1- (4-Sh-acetyl-I- (aminocarbonylmethyl) amino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone, (341) 3 -Ζ- [1 - (4-U-acetyl-H- (piperidin-1-ylcarbonylmethyl) amino) anilino) -1-phenylmethylene] -6methoxycarbonyl-2-indolinone , (342) 3 ^ - [1- (4-Sh-methyl-I- (aminocarbonyl) amino) anilino) -1-phenylmethylene] -6-methoxycarbonyl2-indolinone, (343) 3 ^ - [1- (4- U-methyl-N- (methylaminocarbonyl) amino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone, (344) 3 ^ - [1- (4-U-methyl-I- (dimethylaminocarbonyl) amino) anilino) -1-phenylmethylene] -6-methoxy Arbonyl-2-indolinone, (345) 3 -Ζ - [1 - (4-Sh-methyl-I- (piperidin-1-ylcarbonyl) amino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone, (346) 3-Ζ - [1 - (4-Shch- (2-ethylaminoethyl) -H-methylsulfonylamino) anilino) -1-phenylmethylene] -6methoxycarbonyl-2-indolinone, (347) 3 ^ - [1- (4 -CH-(2-diethylaminoethyl) -Y-methylsulfonylamino) anilino) -1-phenylmethylene] -6 methoxycarbonyl-2-indolinone, (348) 3 - [1 - (4-Sh- (2-pyrrolidin-1-ylethyl ) -Y-methylsulfonylamino) anilino) -1-phenylmethylene] -6methoxycarbonyl-2-indolinone, (349) 3-Ζ- [1 - (4- (K- (2-piperidin-1-ylethyl) -N-methylsulfonylamino) anilino) -1-phenylmethylene] -6methoxycarbonyl-2- indolinone, (350) 3 -Ζ- [1 - (4-Sch- (2-piperazin-1-ylethyl) -Y-methylsulfonylamino) anilino) -1-phenylmethylene] -6methoxycarbonyl-2-indolinone, (351) 3 - Ζ- [1 - (4-Sch- (2- (4-morpholin-1-yl) ethyl) -Y-methylsulfonylamino) anilino) -1-phenylmethylene] 6-methoxycarbonyl-2-indolinone, (352) 3 -Ζ - [1 - (4-Sch- (ethylaminocarbonylmethyl) -Y-methylsulfonylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone, (353) 3 -Ζ- [1- (4- (L- ( diethylaminocarbonylmethyl) -N-methylsulfonylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone, (354) 3 -Ζ- [1 - (4-Shch- (pyrrolidin-1-ylcarbonylmethyl) -Y-methylsulfonylamino) anilino) -1-phen ylmethylene] -6-methoxycarbonyl-2-indolinone, (355) 3 -Ζ - [1- (4-Sch- (piperidin-1-ylcarbonylmethyl) -Y-methylsulfonylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl- 2-indolinone, (356) 3 -Ζ- [1 - (4-Sh- (piperazin-1-ylcarbonylmethyl) -Y-methylsulfonylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone, (357) 3 ^ - [1- (4-Sch - - ((morpholin-4-yl) carbonylmethyl) -Y-methylsulfonylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone, (358) 3 ^ - [1 - (4- (2-dimethylaminoethoxy) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone, (359) 3 -Ζ- [1 - (4- (3-dimethylaminopropoxy) anilino) -1-phenylmethylene] -6-meth hydroxycarbonyl-2-indolinone,

- 70 006080 (360) 3 ^ - [1- (4- (aminocarbonylmethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone, (361) 3 ^ - [1- (4- (2-aminocarbonylethyl ) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone, (362) 3 ^ - [1- (4- (pyridin-2-yl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2- indolinone, (363) 3 ^ - [1- (4- (pyridin-3-yl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone, (364) 3-Ζ- [1 - (4 ( (No. phenetyl-I-methylamino) methyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2indolinone, (365) 3-Ζ- [1 - (4- (No. acetyl-I-methylamino) anilino) -1- phenylmethylene] -6-methoxycarbonyl-2-indolinone, (366) 3 ^ - [1- (4- (N-ethylcarbonyl-H- (dimethylaminocar onylmethyl) amino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone, (367) 3-Ζ- [1 - (4- (#methyl-N-methylsulfonylamino) anilino) -1-phenylmethylene] -6 -methoxycarbonyl2-indolinone, (368) 3 -Ζ- [1 - (4-carboxymethylanilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone, (369) 3 -Ζ- [1- (4-carbamoylmethylanilino) - 1-phenylmethylene] -6-methoxycarbonyl-2-indolinone, (370) 3 ^ - [1- (4-dimethylcarbamoylmethylanilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone, (371) 3 -Ζ- [1 - (4-tetrazol-5 -ilanilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone, (372) 3 -Ζ- [1 - (4- (piperidin-1-ylmethyl) anilino) methylene] -6 methoxytic rbonyl-2-indolinone, (373) 3 -Ζ- [1 - (4- (piperidin-1-ylmethyl) anilino) ethylidene] -6-methoxycarbonyl-2-indolinone, (374) 3 -Ζ- [1 - ( 4- (piperidin-1-ylmethyl) anilino) propylidene] -6-methoxycarbonyl-2-indolinone, (375) 3 -Ζ- [1 - (4- (piperidin-1-ylmethyl) anilino) butylidene] -6-methoxycarbonyl -2-Indolinone, (376) 3 ^ - [1- (4- (No. (3-dimethylaminopropyl) -Y-acetylamino) anilino) methylene] -6-methoxycarbonyl2-indolinone, (377) 3 ^ - [1- ( 4- (No. (3-dimethylaminopropyl) -Y-acetylamino) anilino) ethylidene] -6-methoxycarbonyl-2-indolinone, (378) 3 ^ - [1- (4- (No. (3-dimethylaminopropyl) -N-acetylamino ) anilino) propylidene] -6-methoxycarbonyl-2-indolinone, (379 ) 3 ^ - [1- (4- (No. (3-dimethylaminopropyl) -H-acetylamino) anilino) butylidene] -6-methoxycarbonyl-2-indolinone, (380) 3 ^ - [1- (4- (No. ( 2-dimethylaminoethyl) -Y-methylsulfonylamino) anilino) methylene] -6-methoxycarbonyl-2-indolinone, (381) 3 ^ - [1- (4- (No. (2-dimethylaminoethyl) -Y-methylsulfonylamino) anilino) ethylidene] -6-methoxycarbonyl-2-indolinone, (382) 3 ^ - [1- (4- (No. (2-dimethylaminoethyl) -N-methylsulfonylamino) anilino) propylidene] -6-methoxycarbonyl-2-indolinone, (383) 3 -Ζ- [1 - (4- (No. (2-dimethylaminoethyl) -Y-methylsulfonylamino) anilino) butylidene] -6-methoxycarbonyl-2-indolinone, (384) 3 -Ζ- [1 - (4-tetrazole-5 -ilanilino) methylene] -6 -methoxycarbonyl-2-indolinone, (385) 3 ^ - [1- (4-tetrazol-5-ylanilino) ethylidene] -6-methoxycarbonyl-2-indolinone, (386) 3-[- [1 - (4-tetrazole -5 -ilanilino) propylidene] -6-methoxycarbonyl-2-indolinone, (387) 3 -Ζ- [1 - (4-tetrazol-5 -ilanilino) butylidene] -6-methoxycarbonyl-2-indolinone, (388) 3 -Ζ- [1- (4-carboxyanilino) methylene] -6-methoxycarbonyl-2-indolinone, (389) 3 -Ζ- [1 - (4-carboxyanilino) ethylidene] -6-methoxycarbonyl-2-indolinone, (390 ) 3 -Ζ- [1- (4-carboxyanilino) propylidene] -6-methoxycarbonyl-2-indolinone, (391) 3 -Ζ- [1 - (4-carboxyanilino) butylidene] -6-methoxycarbonyl-2-indolinone, (3 92) 3 -Ζ- [1 - (4- (No.Benzyl-I-methyl nomethyl) anilino) -1-methylmethylene] -6-methoxycarbonyl-2indolinone, (393) 3 ^ - [1- (4- (2,3,4,5-tetrahydrobenzo (b) azepin-3-ylmethyl) anilino) - 1-methylmethylene] -6-methoxycarbonyl-2-indolinone, (3 94) 3 -Ζ- [1 - (4 - ((benzo (1,3) dioxol-5-ylmethyl) methylaminomethyl) anilino) -1-methylmethylene] -6 methoxycarbonyl-2-indolinone, (395) 3 -Ζ- [1 - (4- (No.phenethyl-N-methylaminomethyl) anilino) -1-methylmethylene] -6-methoxycarbonyl-2indolinone, (396) 3 ^ - [1 - (4- (no. (3,4-dimethoxybenzyl) -H-methylaminomethyl) anilino) -1-methylmethylene] -6-methoxycarbonyl-2-indolinone, (3 97) 3 -Ζ- [1 - (4- (Y - (4-chlorobenzyl) -H-methylaminomethyl) anilino) -1-methylmethylene] -6-metho Xycarbonyl-2-indolinone, (398) 3 ^ - [1- (4- (No. (4-methylbenzyl) -Y-methylaminomethyl) anilino) -1-methylmethylene] -6-methoxycarbonyl-2-indolinone, (399) 3 -Ζ- [1- (4- (No. (4-fluorobenzyl) -H-methylaminomethyl) anilino) -1-methylmethylene] -6-methoxycarbonyl-2-indolinone,

- 71 006080 (400) 3 -Ζ- [1 - (4- (No. (4-bromobenzyl) -Nomethylaminomethyl) anilino) -1-methylmethylene] -6-methoxycarbonyl-2-indolinone, (401) 3 ^ - [ 1- (4- (No. (3-dimethylaminopropionyl) -№dimethylaminocarbonylmethylamino) anilino) -1phenylmethylene] -6-methoxycarbonyl-2-indolinone, (402) 3 ^ - [1- (4- (No. (4-dimethylaminobutyryl) - Dimethylaminocarbonylmethylamino) anilino) -1phenylmethylene] -6-methoxycarbonyl-2-indolinone, (403) 3 ^ - [1- (4- (#dimethylaminocarbonylmethyl-N (2-dimethylaminoethylsulfonyl) amino) anilino) -1-phenylmethylene] -methoxycarbonyl-2-indolinone, (404) 3 ^ - [1- (4- (No. of dimethylaminocarbonylmethyl-No. (3-dimethylaminopropyl lofonyl) amino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone, (405) 3-Ζ - [1 - (4 - ((2-hydroxyethyl) aminomethyl) anilino) -1-phenylmethylene] -6 -methoxycarbonyl-2 indolinone, (406) 3 -Ζ- [1 - (4 - ((2-methoxyethyl) aminomethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2indolinone, (407) 3 -Ζ- [1 - (4 - ((2-dimethylaminoethyl) aminomethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl2-indolinone, (408) 3 -Ζ- [1 - (4 - ((3-dimethylaminopropyl) aminomethyl) anilino) -1 -phenylmethylene] -6-methoxycarbonyl-2-indolinone, (409) 3 ^ - [1- (4 - ((No. tert-butoxycarbonyl-2-aminoethyl) aminomethyl) anilino) -1-phenylmethylene] -6 methoxycarbonyl- 2-indolinone, (410) 3 ^ - [1- (4 - ((No. tert-butoxycarbonyl-3-aminopropyl) aminomethyl) anilino) -1-phenylmethylene] 6-methoxycarbonyl-2-indolinone, (411) 3 -Ζ - [1 - (4 - ((2-aminoethyl) aminomethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone, (412) 3 ^ - [1- (4 - ((3-aminopropyl) aminomethyl ) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2indolinone, (413) 3-Ζ- [1 - (4 - ((2-acetylaminoethyl) aminomethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2indolinone, (414) 3 -Ζ- [1 - (4 - ((3-acetylaminopropyl) aminomethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone, (415) 3 ^ - [1- (4- ( (2-methylsulfonylaminoethyl) aminomethyl) an Eno) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone, (416) 3 ^ - [1- (4 - ((3-methylsulfonylaminopropyl) aminomethyl) anilino) -1-phenylmethylene] -6 methoxycarbonyl-2-indolinone, (417) 3 -Ζ- [1 - (4- (No. (no. Of t-butoxycarbonyl-2-aminoethyl) -Nomethylaminomethyl) anilino) -1 phenylmethylene] -6-methoxycarbonyl-2-indolinone, (418) 3 -Ζ - [1 - (4- (No. (2-aminoethyl) -Nomethylaminomethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone, (419) 3 -Ζ- [1 - (4- (No. ( 2-acetylaminoethyl) -Nomethylaminomethyl) anilino) -1-phenylmethylene] -6methoxycarbonyl-2-indolinone, (420) 3 ^ - [1- (4- (No. (2-methylsulfonylaminoethyl) -Nomethylaminomethyl) anilino) -1- f enylmethylene] 6-methoxycarbonyl-2-indolinone, (421) 3 -Ζ- [1 - (4- (carboxymethylaminomethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2indolinone, (422) 3 ^ - [1- ( 4- (ethoxycarbonylmethylaminomethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl2-indolinone, (423) 3 -Ζ- [1 - (4- (carbamoylmethylaminomethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2indolinone ( 424) 3 ^ - [1- (4- (dimethylcarbamoylmethylaminomethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone, (425) 3 -Ζ- [1- (4- (methylcarbamoylmethylaminomethyl) anilino) -1 -phenylmethylene] -6-methoxycarbonyl2-indolinone, (426) 3 ^ - [1- (4- (No. of dimethylaminomethyl rbonyl-метmethylamino) -3-aminoanilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone, (427) 3 ^ - [1- (4- (No.dimethylaminomethylcarbonyl-No.methylamino) -3-nitroanilino) -1 -phenylmethylene] -6-methoxycarbonyl-2-indolinone, (428) 3 -Ζ- [1- (4- (No. of dimethylaminomethylcarbonyl-No.methylamino) -3-acetylaminoanino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone , (429) 3 -Ζ- [1- (4- (No. dimethylaminomethylcarbonyl-No.methylamino) -3-methylsulfonylaminoanilino) 1-phenylmethylene] -6-methoxycarbonyl-2-indolinone, (430) 3 -Ζ- [1 - ( 4- (No. dimethylaminomethylcarbonyl-No. methylamino) -3-cyanoanilino) -1-phenylmethylene] -6-methoxycarb onil-2-indolinone,

- 72 006080 (431) 3 ^ - [1- (4- (No.dimethylaminomethylcarbonyl-No.methylamino) -3-hydroxyanilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone, (432) 3 -Ζ- [1 - (4- (No. dimethylaminomethylcarbonyl-No. methylamino) -3-methoxyanilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone, (433) 3 -Ζ- [1 - (4- (No. of dimethylaminomethylcarbonyl-No. methylamino) -3-ethoxycarbonylanilino) -1phenylmethylene] -6-methoxycarbonyl-2-indolinone, (434) 3 -Ζ- [1 - (4- (No. dimethylaminomethylcarbonyl-No.methylamino) -3 -carboxyanilino) -1-phenylmethylene] -6- methoxycarbonyl-2-indolinone, (435) 3 -Ζ- [1- (4- (No.dimethylaminomethylcarbonyl-No.methylamino) -3 -carb Moylanilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone, (436) 3 -Ζ- [1- (4- (No. of dimethylaminomethylcarbonyl-No.methylamino) -3-chloroanilino) -1 -phenylmethylene] 6-methoxycarbonyl- 2-indolinone, (437) 3 -Ζ- [1 - (4- (No. dimethylaminomethylcarbonyl-No. methylamino) -3-fluoroanilino) -1-phenylmethylene] -

6-methoxycarbonyl-2-indolinone, (438) 3 ^ - [1- (4- (No. of dimethylaminomethylcarbonyl-No.methylamino) -3-bromoanilino) -1-phenylmethylene] 6-methoxycarbonyl-2-indolinone, (439) 3 - Ζ- [1- (4- (No. dimethylaminomethylcarbonyl-No. methylamino) -3-methylanilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone, (440) 3 ^ - [1- (4- (No. of dimethylaminomethylcarbonyl- No. methylamino) -3-trifluoromethylanilino) -1phenylmethylene] -6-methoxycarbonyl-2-indolinone, (441) 3 -Ζ- [1 - (4- (No.dimethylaminomethylcarbonyl-No.methylamino) -3,5-dibromanilino) -1- phenylmethylene] -6-methoxycarbonyl-2-indolinone, (442) 3 -Ζ- [1 - (4- (No. of dimethylaminomethylcarbonyl-No. methyls but) -3,5-dichloroanilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone, (443) 3 -Ζ- [1 - (4- (dimethylaminomethyl) -3-aminoanilino) -1-phenylmethylene] - 6-methoxycarbonyl-2 indolinone, (444) 3 -Ζ- [1 - (4- (dimethylaminomethyl) -3-nitroanilino) -1-phenylmethylene] -6-methoxycarbonyl-2indolinone, (445) 3 -Ζ- [1 - ( 4- (dimethylaminomethyl) -3-acetylaminoanilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone, (446) 3 ^ - [1- (4- (dimethylaminomethyl) -3-methylsulfonylaminoanilino) -1-phenylmethylene] - 6-methoxycarbonyl-2-indolinone, (447) 3 -Ζ- [1 - (4- (dimethylaminomethyl) -3 -cyanoanilino) -1-phenylmethylene] -6-methoxycarbonyl-2indolinone, (448) 3 -Ζ- [1- (4- (dimethylaminomethyl) -3-hydroxyanilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone, (449) 3 ^ - [1- (4- (dimethylaminomethyl) -3-methoxyanilino) -1-phenylmethylene] -6-methoxycarbonyl-2indolinone, (450) 3 ^ - [1- (4- (dimethylaminomethyl) -3-ethoxycarbonylanilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone , (451) 3 -Ζ- [1- (4- (dimethylaminomethyl) -3 -carboxyanilino) -1-phenylmethylene] -6-methoxycarbonyl-2indolinone, (452) 3 -Ζ- [1- (4- (dimethylaminomethyl) -3 -carbamoylanilino) -1-phenylmethylene] -6-methoxycarbonyl2-indolinone, (453) 3 -Ζ- [1 - (4- (dimethylaminomethyl) -3-chloroanilino) -1-phenylmethylene] -6-methox carbonyl-2 indolinone, (454) 3 ^ - [1- (4- (dimethylaminomethyl) -3-fluoroanilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone, (455) 3 ^ - [1- (4- (dimethylaminomethyl) -3-bromoanilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone, (456) 3 -Ζ- [1 - (4- (dimethylaminomethyl) -3-methylanilino) -1-phenylmethylene] -6 -methoxycarbonyl-2 indolinone, (457) 3 -Ζ- [1 - (4- (dimethylaminomethyl) -3-trifluoromethylanilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone, (458) 3 -Ζ- [1 - (4-dimethylaminomethyl-3,5-dibromanilino) -1-phenylmethylene] -6-methoxycarbonyl-2indolinone, (459) 3 -Ζ- [1 - (4- (dimethylaminomethyl) -3,5-dichloranilino) -1-phenylmethylene ] -6-methoxycarbonyl-2-indolinone, (460) 3 ^ - [1- (4- (dimethylaminomethyl) anilino) -1-phenylmethylene] -6 - [(2-hydroxyethoxy) carbonyl] -2 -indolinone, (461) 3 ^ - [1- (4- (dimethylaminomethyl) anilino) -1-phenylmethylene] -6 - [(ethoxycarbonylmethoxy) carbonyl] -2-indolinone,

- 73 006080 (462) 3 ^ - [1- (4- (dimethylaminomethyl) anilino) -1-phenylmethylene] -6 - [(carboxymethoxy) carbonyl] -2indolinone, (463) 3 -Ζ- [1 - (4- (dimethylaminomethyl) anilino) -1-phenylmethylene] -6 - [(carbamoylmethoxy) carbonyl] 2-indolinone, (464) 3 -Ζ- [1 - (4- (No.dimethylaminomethylcarbonyl-No.methylamino) anilino) -1-phenylmethylene] -6 - [(2hydroxyethoxy) carbonyl] -2-indolinone, (465) 3 -Ζ- [1 - (4- (No.dimethylaminomethylcarbonyl-No.methylamino) anilino) -1-phenylmethylene] -6 [(ethoxycarbonylmethoxy) carbonyl] - 2-indolinone, (466) 3 -Ζ- [1 - (4- (No. dimethylaminomethylcarbonyl-No.methylamino) anilino) -1-phenylmethylene] -6 [(carboxymethoxy) carbonyl] -2-Indolinone, (467) 3 -Ζ- [1 - (4- (No.dimethylaminomethylcarbonyl-No.methylamino) anilino) -1-phenylmethylene] -6 [(carbamoylmethoxy) carbonyl] -2-indolinone, (468) 3 - Ζ- [1- (4- (No. dimethylaminomethylcarbonyl-No. methylamino) anilino) -1-phenylmethylene] -6 - [(2methoxyethoxy) carbonyl] -2-indolinone, (469) 3 -Ζ- [1 - (4- ( C-dimethylaminomethylcarbonyl-No.methylamino) anilino) -1-phenylmethylene] -6 - [(2dimethylaminoethoxy) carbonyl] -2-indolinone, (470) 3 ^ - [1- (4- (No.dimethylaminomethylcarbonyl-No.methylamino) anilino) - 1-phenylmethylene] -6 - [(2- (no. Tert-butoxycarbonylamino) ethoxy) carbonyl] -2-indolinone, (471) 3 -Ζ- [1 - (4- (C-dimethylaminomethylcarb onyl-methylamino) anilino) -1-phenylmethylene] -6 - [(2aminoethoxy) carbonyl] -2-indolinone, (472) 3 -Ζ- [1 - (4- (No.dimethylaminomethylcarbonyl-No.methylamino) anilino) -1 -phenylmethylene] -6 [(2,2,2-trifluoroethoxy) carbonyl] -2-indolinone, (473) 3 ^ - [1- (4- (No. ((4-methylpiperazin-1-yl) methylcarbonyl) -N methylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone, (474) 3 -Ζ- [1 - (4- (No. (imidazo-1-ylmethylcarbonyl) -№methylamino) anilino) -1-phenylmethylene ] -6methoxycarbonyl-2-indolinone, (475) 3 -Ζ- [1 - (4- (C- (phthalimido-2-ylmethylcarbonyl) -№methylamino) anilino) -1-phenylmethylene] -6methoxycarbonyl-2-indolinone, ( 476) 3 ^ - [1- (4- (No. Ethylcarbonyl-Nmethylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone, (477) 3 -Ζ- [1 - (4- (C-acetylaminomethylcarbonyl-Nmethylamino) anilino) -1-phenylmethylene] - 6 methoxycarbonyl-2-indolinone, (478) 3 ^ - [1- (4- (#methylsulfonylaminomethylcarbonyl-No.methylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone, (479) 3 -Ζ- [1 - (4- (C - ((No. (2-methoxyethyl) -Nomethylamino) methylcarbonyl) -Nomethylamino) anilino) -1 phenylmethylene] -6-methoxycarbonyl-2-indolinone, (480) 3 ^ - [1- ( 4- (No. ((No. (2-dimethylaminoethyl) -Nomethylamino) methylcarbonyl) -Nomethylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2 ndolinolin, (481) 3 -Ζ- [1 - (4- (C - ((di- (2-hydroxyethyl) amino) methylcarbonyl) -Mmethylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone , (482) 3 -Ζ- [1 - (4-tert-butoxycarbonylmethylanilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone, (483) 3 ^ - [1- (4- (C-dimethylaminomethylcarbonyl-No. Methylamino) anilino) methylene] -6-methoxycarbonyl-2-indolinone, (484) 3 -Ζ- [1 - (4- (#dimethylaminomethylcarbonyl-№methylamino) anilino) ethylidene] -6-methoxycarbonyl-2-indolinone, (485 ) 3 ^ - [1- (4- (No. dimethylaminomethylcarbonyl-No.methylamino) anilino) propylidene] -6-methoxycarbonyl-2-indolinone, (486) 3 -Ζ- [1 - (4- (No.dimethyl Momethylcarbonyl-Methyllamino) anilino) butylidene] -6-methoxycarbonyl-2-indolinone, (487) 3 -Ζ- [1 - (4- (dimethylaminomethyl) anilino) methylene] -6-methoxycarbonyl-2-indolinone, (488) 3 ^ - [1- (4- (dimethylaminomethyl) anilino) ethylidene] -6-methoxycarbonyl-2-indolinone, (489) 3 ^ - [1- (4- (dimethylaminomethyl) anilino) propylidene] -6-methoxycarbonyl-2 β-indolinone, (490) 3 ^ - [1- (4- (dimethylaminomethyl) anilino) butylidene] -6-methoxycarbonyl-2-indolinone, (491) 3-Ζ- [1 - (4-tert-butyloxycarbonylanilino) -1 -phenylmethylene] -6-methoxycarbonyl-2-indolinone, (492) 3 ^ - [1- (4- (no. (2-dimethylaminoethyl) -№methylamino) anilino) -1-phenylmethylene] -6 -methoxycarbonyl-2-indolinone, (493) 3 -Ζ- [1 - (4- (Ν- (3-dimethylaminopropyl) -Nmethylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone, (494 ) 3 -Ζ- [1 - (4- (#methyl acetylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone, (495) 3 -Ζ- [1 - (4- (imidazol-4-yl ) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone,

- 74 006080 (496) 3 -Ζ- [1 - (4 - ((no. (Dioxolan-2-ylmethyl) -Nomethylamino) methyl) anilino) -1-phenylmethylene] -6methoxycarbonyl-2-indolinone, (497) 3 -Ζ- [1 - (4- (No.benzyl-No.methylaminomethyl) anilino) -1-methylmethylene] -6-carbamoyl-2-indolinone, (498) 3-Ζ- [1 - (4- (2,3, 4,5-tetrahydrobenzo (b) azepin-3-ylmethyl) anilino) -1-methylmethylene] -6-carbamoyl-2-indolinone, (499) 3 -Ζ- [1 - (4 - ((benzo (1,3 ) dioxol-5-ylmethyl) methylaminomethyl) anilino) -1-methylmethylene] -6carbamoyl-2-indolinone, (500) 3 -Ζ- [1 - (4- (No.phenethyl-No.methylaminomethyl) anilino) -1-methylmethylene] -6-carbamoyl-2-indolinone, (501) 3 -Ζ- [1- (4- (Ν- (3,4-dimethoxybenzyl) -Nomethylaminomethyl) anilino) -1 -methylmethylene] -6-carbamoyl-2-indolinone, (502) 3 -Ζ- [1- (4- (No. (4-chlorobenzyl) -Nmethylaminomethyl) anilino) -1 -methylmethylene] -6-carbamoyl-2indolinone, (503) 3 ^ - [1- (4- (No. (4-methylbenzyl) -Nomethylaminomethyl) anilino) -1-methylmethylene] -6-carbamoyl-2indolinone, (504) 3 -Ζ- [1- (4- (No. (4-fluorobenzyl) -Nomethylaminomethyl) anilino) -1-methylmethylene] -6-carbamoyl-2indolinone, (505) 3 ^ - [1- (4- (C- (4-bromobenzyl) -№methylaminomethyl) anilino ) -1-methylmethylene] -6-carbamoyl-2indolinone, (506) 3 ^ - [1- (4 - ((no. (2-methoxyethyl) -N.methylamino) methyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl -2-Indolinone, (507) 3 ^ - [1- (4- (dimethylaminomethyl) anilino) -1-phenylm ethylene] -6 - [(2-aminoethoxy) carbonyl] -2indolinone, (508) 3 -Ζ- [1 - (4 - ((Ν- (3-methylsulfonylaminopropyl) -Nomethylamino) methyl) anilino) -1-phenylmethylene ] -6-methoxycarbonyl-2-indolinone.

Example 13. A vial with a dry preparation containing 75 mg of active ingredient per 10 ml.

Composition:

Active ingredient 75.0 mg

Mannitol 50.0 mg

Water for injection Up to 10.0 ml

Receiving:

The active ingredient and mannitol are dissolved in water. After packaging, the solution is lyophilized. Ready for use solution is obtained by dissolving in water for injection.

Example 14. A vial with a dry preparation containing 35 mg of active ingredient per 2 ml.

Composition:

Active ingredient 35.0 mg

Mannitol 100.0 mg

Water for injection Up to 2.0 ml

Receiving:

Example 15. Tablet with 50 mg of active ingredient.

Composition:

(1) Active ingredient 50.0 mg (2) Lactose 98.0 mg (3) Corn starch 50.0 mg (4) Polyvinylpyrrolidone 15.0 mg (5) Magnesium stearate 2.0 mg

215.0 mg

Receiving:

Ingredient (1) is mixed with ingredients (2) and (3) and the mixture is granulated using an aqueous solution of ingredient (4). Ingredient (5) is admixed to the dried granulate. From this mixture pressed biased tablets with a double-sided facet and one-sided notch.

Tablet diameter: 9 mm.

Example 16. Tablet with 350 mg of active ingredient.

Composition:

(1) Active ingredient 350.0 mg (2) Lactose 136.0 mg (3) Cornstarch 80.0 mg (4) Polyvinylpyrrolidone 30.0 mg (5) Magnesium stearate 4.0 mg

600.0 mg

- 75 006080

Receiving:

Tablet diameter: 12 mm.

Example 17. Capsules with 50 mg of active ingredient.

Composition:

(1) Active ingredient 50.0 mg (2) Corn starch, dried 58.0 mg (3) Lactose, powder 50.0 mg (4) Magnesium stearate 2.0 mg

160.0 mg

Receiving:

Ingredient (1) is ground together with ingredient (3). To this obtained by rubbing the mixture with vigorous stirring, add a mixture of ingredients (2) and (4). At the end of this powder mixture is packaged in a machine for filling capsules in solid-gelatin detachable capsules of size 3.

Example 18. Capsules with 350 mg of active ingredient.

Composition:

(1) Active ingredient 350.0 mg (2) Corn starch, dried 46.0 mg (3) Lactose, powder 30.0 mg (4) Magnesium stearate 4.0 mg

430.0 mg

Receiving:

Ingredient (1) is ground together with ingredient (3). To this obtained by rubbing the mixture with vigorous stirring, add a mixture of ingredients (2) and (4). At the end of this powder mixture is packaged in a machine for filling capsules in solid-gelatin detachable capsules of size 0.

Example 19. Suppositories with 100 mg of active ingredient.

Composition 1 candles:

Active ingredient 100.0 mg

Polyethylene glycol (MM 1500) 600.0 mg

Polyethylene glycol (MM 6000) 460.0 mg

Polyethylene sorbitan monostearate 840.0 mg

2000.0 mg

Receiving:

Polyethylene glycol is melted together with polyethylene sorbitan monostearate. At 40 ° C, the ground active substance is dispersed homogeneously in the resulting molten mass. After that, the molten mass is cooled to 38 ° C and poured into pre-slightly cooled forms for suppositories.

Claims

CLAIM

1. Substituted in position 6 of the indolinone of the General formula

but.

wherein

X means an oxygen or sulfur atom,

R1 represents a hydrogen atom or a prodrug radical, such as C1 _-4 -alkoxycarbonyl or C _2-4 -alkanoyl,

K2 means a carboxy group, a linear or branched C1-6 alkoxycarbonyl group, C4-7 a cycloalkoxycarbonyl or aryloxycarbonyl group,

- 76 006080 linear or branched C _1-6 alkoxycarbonyl group, the alkyl fragment of which is substituted at the terminal position by phenyl, heteroaryl, carboxy group, C _1-3 alkoxycarbonyl, aminocarbonyl, C1-3 alkyl amino aminocarbonyl or di- (C1-3 alkyl) aminocarbonyl, linear or ramidinamide, carbonyl or amino (C1-3 alkyl) aminocarbonyl, linear or branched C _2-6 alkoxycarbonyl group, the alkyl fragment of which is substituted in the terminal position by a chlorine atom, hydroxy group, C _1-3 alkoxy group, amino group, C _1-3 alkylamino group or di (C _1-3 alkyl) amino group, aminocarbonyl or methylaminocarbonyl your group, optionally substituted in position 2 of an ethyl group by a hydroxy group or a C1-3 alkoxy group of an ethylaminocarbonyl group, or if K ₄ does not mean aminosulfonylphenyl or K (C1 _-5 alkyl) -C1 _-3 alkylaminocarbonylphenyl, also means a di- (C1-2 alkyl) aminocarbonyl group ,

K ₃ is hydrogen, C1 _-6 alkyl, _C3-7 cycloalkyl, trifluoromethyl or heteroaryl, phenyl, or naphthyl mono- or disubstituted by fluorine, chlorine, bromine or iodine, trifluoromethyl, _{C! -3} alkyl or C _1-3 alkoxy group is phenyl or naphthyl; in the case of substitution by two groups, the substituents may be identical or different and the indicated unsubstituted as well as mono- and disubstituted phenyl and naphthyl may additionally be substituted by hydroxy group, hydroxy-C1 _-3 alkyl or C1 _-3 alkoxy-C1 _-3 alkyl, cyano, carboxy, carboxy-C _1-3 alkyl C _1-3 alkoxycarbonyl, aminocarbonyl, C1-3 alkylaminocarbonyl or di- (C1-3 alkyl) aminocarbonyl, nitro, amino, C1 _-3 alkylamino, di- (C1 _-3 alkyl) amino or amino-C1 _-3 alkyl,

C1 _-3 alkylcarbonylamino, K (C1 _-3 alkyl) -C1 _-3 alkylcarbonylamino group, a C1 _-3 alkylcarbonylamino-C1 _-3 alkyl, R (C1 _-3 alkyl) -C1 _-3 alkylcarbonylamino-C1 _-3 alkyl, C1 _-3 alkylsulfonylamino C1 _-3 alkylsulfonylamino-C1 _-3 alkyl, R (C1 _-3 alkyl) -C1 _-3 alkylsulfonylamino-C1 _-3 alkyl or aryl-C _1-3 alkylsulfonylamino, cycloalkylamino tsikloalkileniminogruppoy, tsikloalkileniminokarbonilom, tsikloalkilenimino-C1 _-3 alkyl, tsikloalkileniminokarbonil-C1 _-3 alkyl or tsikloalkileniminosulfonilS _1-3 alkyl, in each case with 4-7 MEMBER s rings, wherein each of the methylene groups in position 4 in a 6- or 7-membered tsikloalkileniminogruppe can be replaced by oxygen or sulfur atom, sulfinyl, sulfonyl, -ΝΉ- or -MC _1-3 alkyl) -, heteroaryl or heteroaryl, or -C1 _-3 alkyl,

K4 is C3-7 cycloalkyl, wherein the methylene group in position 4 of the 6- or 7-membered cycloalkyl group may be substituted by an amino group, a C1-3 alkylamino group or a di- (C1-3 alkyl) amino group or replaced by -Ν4- or -MS _1-3 alkyl) -, or substituted by a K ₆ group, phenyl, which may additionally be mono- or disubstituted with a fluorine, chlorine, bromine or iodine atom, C1 _-5 alkyl, trifluoromethyl, hydroxy, C _{! -3} alkoxy, carboxy, C1 _-3 alkoxycarbonyl, amino group, acetylamino group, C1 _-3 alkylsulfonylamino group, aminocarbonyl, C _{1- 3} alkylaminocarbonyl, di- (C _1-3 alkyl) aminocarbonyl, aminosulfonyl, C _1-3 alkylaminosulfonyl, di- (C _1-3 alkyl) aminosulfonyl, nitro group or cyano group, while the substituents may be identical or different and

K6 means a hydrogen atom, fluorine, chlorine, bromine or iodine, cyano, nitro, amino, C1-5 alkyl, C3-7cycloalkyl, trifluoromethyl, phenyl, tetrazolyl or heteroaryl, a group of the formula in which the atoms of hydrogen bonded to the nitrogen atom are independently in each case another may be replaced by C1 _-3 alkyl, C1 _-3 alkoxy, C1 _-3 alkoxy-C1 _-3 alkoxy, phenyl-C 1 _-3 alkoxy, amino S2-3alkoksigruppu, S1-3alkilamino S2-3alkoksigruppu-di- ( C 1-3 alkyl) amino-S2-3alkoksigruppu, phenyl-C1 _-3 alkilaminoS _2-3 alkoxy, R (C1 _-3 alkyl) phenyl-C1 _-3 alkylamino C _2-3 alkoxy group, C5-7 cycloalkylenimino-C2-3 alkoxy group or C1-3 alkyl mercapto group, carboxy group, C1-4 alkoxycarbonyl, aminocarbonyl, C1 _-3 alkylaminocarbonyl, K (C1 _-5 alkyl) -C1 _-3 alkylaminocarbonyl, phenyl-C1-C1 -C1 -C alkyl and C 1 _-3 alkylaminocarbonyl, phenyl-1-C 1 _-3 alkoxycarbonyl, phenyl-1-C 1 _-3 alkoxycarbonyl alkylaminocarbonyl, K (C 1 _-3 alkyl) phenyl-C 1 _-3 alkylaminocarbonyl, piperazinocarbonyl or Ν (C 1 _-3 alkyl) piperazinocarbonyl, C 1 _-3 alkylaminocarbonyl or K (C 1 _-5 alkyl-C 1 _-3 alkylaminocarbonyl, in which the alkyl fragment is substituted with a car or C _1-3 alkoxycarbonyl or in position 2 or 3 is substituted by a di (C1 _-3 alkyl) amino group, piperazinogr upa, K (C1 _-3 alkyl) piperazino group or 47-membered cycloalkylenimino group, C _3-7 cycloalkylcarbonyl,

- 77 006080 wherein the methylene group in position 4 of a 6- or 7-membered cycloalkyl moiety may be substituted by amino, C1 _-3 alkylamino or di (C1 _-3 alkyl) amino or substituted by -ΝΗ- or - ^ C1 _-3 alkyl ) -,

A 4-7 membered cycloalkylenimino group in which the methylene group bound to the imino group can be replaced by carbonyl or sulfonyl, or the cycloalkylene moiety can be condensed with a phenyl ring, or one or two hydrogen atoms in each case can be replaced by C1-3 alkyl, and / or the methylene group in each case in the 4 position 6- or 7-membered tsikloalkileniminogruppy may be substituted with carboxy, C1 _-3 alkoxycarbonyl, aminocarbonyl, C1 _-3 alkylaminocarbonyl, di (C1 _-3 alkyl) aminocarbonyl, phenyl-C1 _-3 alkyl nogruppoy or N- (C1 _-3 alkyl) or phenyl-S1-3alkilaminogruppoy replaced by oxygen or sulfur atom, sulfinyl, sulfonyl, -ΝΗ-, -N (C1 _-3 alkyl) -, -N (phenyl) -, -N (C1 _-3 alkylcarbonyl) - or -Y (benzoyl) -, substituted by the group H ₇ C1 _-4 alkyl, where

H7 means

C3-7 cycloalkyl, wherein a methylene group in position 4 of a 6- or 7-membered cycloalkyl group may be substituted by amino, C1 _-3 alkylamino or di (C1 _-3 alkyl) amino or substituted by -ΝΗili -N (C1 _-3 alkyl ) - or in a 5-7-membered cycloalkyl group, the group - (CH ₂ ) ₂ - can be replaced by the group -CO-ΝΗ-, the group - (CH ₂ ) ₃ - can be replaced by the group -ΝΗ-ί, Ό- ΝΗ- or -CO-ΝΗ-CO- or the group - (CH ₂ ) ₄ - can be replaced by the group -NΗ-CO-NΗ-CO-, in each case the hydrogen atom bound to the nitrogen atom can be replaced by C1 _-3 alkyl, aryl or het Roar, hydroxy or C1 _-3 alkoxy, amino, C1 _-7 alkylamino, di- (C1 _-7 alkyl) amino, phenylamino, Ν-phenyl-S ^ z alkylamino, phenyl-C1 _-3 alkylamino, N- (C1 _-3 alkyl) phenyl-C1 _-3 alkylamino or di (phenyl-C1-3alkyl) amino, w-hydroxy-C _2-3 alkylamino, N- (C1 _-3 alkyl) -w-hydroxy-C _2-3 alkylamino group, a di- (w-hydroxy-C _2-3 alkyl) amino group, di- (sh- (C1 _-3 alkoxy) -C _2-3 alkyl) amino group or N- (dioxolan-2-yl) -C1 _-3 alkylamino group, C1- 3alkilkarbonilamino-S2-3alkilaminogruppu or S1-3alkilkarbonilamino-S2-3alkil-N- (C1 _-3 and keel) amino group,

C1 _-3 alkylsulfonylamino, N- (C1 _-3 alkyl) -C1 _-3 alkylsulfonylamino, _{C! -3-alkylsulfonylamino} C _2-3 alkylamino, or C1 _{-3-alkylsulfonylamino} C _2-3 alkyl-N- (C1 _-3 alkyl) amino, hydroxycarbonyl-C1 _-3 alkylamino or Ν- (C 1 _-3 alkyl) hydroxycarbonyl-C 1 _-3 alkylamino, guanidino, wherein one or two hydrogen atoms in each case may be replaced by C 1-3 alkyl, a group of formula

-Jad-SODODp-u (II), in which

H ₈ means a hydrogen atom or C 1 _-3 alkyl, η means the number 0, 1, 2 or 3 and

H ₉ represents an amino, C _1-4 alkylamino, di- (C _{1 -4} alkyl) amino, phenylamino, N- (C1 _-4 alkyl), phenylamino, benzylamino, N- (C1 _-4 alkyl) benzylamino, or a C1 _-4 alkoxy group , 4-7-membered cycloalkylenimino group, in each case the methylene group in position 4 of the 6- or 7-membered cycloalkylenimino group can be replaced by an oxygen or sulfur atom, sulfinyl, sulfonyl, -ΝΗ-, -Ν (ί. ' _{1- 3} alkyl) -, -N (phenyl) -, -MC _1-3 -alkylcarbonyl) - or -N (benzoyl) - or, if η is the number 1, 2 or 3 also represents a hydrogen atom, a group of the formulas

-ZHNYUMODt-TOO-Np (III), in which

H10 means a hydrogen atom, C1-3 alkyl, C1-3 alkylcarbonyl, arylcarbonyl, phenyl-C1-3 alkylcarbonyl, C1-3 alkylsulfonyl, arylsulfonyl or phenyl-C1-3 alkylsulfonyl, t means 1, 2, 3 or 4, o means 1 or if t means one of the numbers 2, 3, or 4, it also means the number 0 and

H ₁₁ means amino group, C _1-4 alkylamino group, di- (C _1-4 alkyl) amino group, phenylamino group, M- (C 1 _-4 alkyl) phenylamino group, benzylamino group, M- (C 1 _-4 alkyl) benzylamino group, C 1 _-4 alkoxy group or a C1-3 alkoxy-C1-3 alkoxy group optionally substituted in the 1 position with a C1-3 alkyl di (C1-4 alkyl) amino C1-3 alkylamino group or a 4-7 membered cycloalkylenimino group, while the cycloalkylene moiety can be condensed with a phenyl ring or in each case the methylene group in position 4 of a 6- or 7-membered cycloalkylenimino group can be replaced not on an oxygen or sulfur atom, sulfinyl, sulfonal, -ΝΗ-, -MS _1-3 alkyl) -, -Y (phenyl) -, -MS _1-3 alkylcarbonyl) or -Y (benzoyl) -,

- 78 006080

C _4-7 cycloalkylamino, C _4-7 cycloalkyl-C _1-3 alkylamino or C _4-7 cycloalkenylamino group in which the position 1 of the ring does not participate in the formation of a double bond, with these groups being optionally substituted in each case an amino nitrogen atom with C 5-7 cycloalkyl, C 2-4 alkenyl or C _1-4 alkyl,

A 4-7 membered cycloalkylenimino group in which the cycloalkylene moiety can be condensed with a phenyl group or with an optionally substituted fluorine, chlorine, bromine or iodine atom, a nitro group, a C1-3 alkyl, C1-3 alkoxy group or an amino group of an oxazolo, imidazolo, thiazolo, pyridino, pyrazino or pyrimidine group and / or one or two hydrogen atoms in each case can be replaced by C1-3 alkyl, C5-7 cycloalkyl or phenyl and / or methylene group in position 3 of the 5-membered cycloalkylenimino group can be replaced by a hydroxy group, hydro Si-C1 _- Zalkil, C ₁ . ₃ alkoxy group or C 1 _-3 alkoxy-C 1 _-3 alkyl, in each case the methylene group in position 3 or 4 with a 6- or 7-membered cycloalkylamino group can be replaced by hydroxy group, hydroxy-C _1-3 alkyl, C _1-3 alkoxy group, C _1-3 alkoksiS1 _-3 alkyl, carboxy, C1 _-4 alkoxycarbonyl, aminocarbonyl, C1 _-3 alkylaminocarbonyl, di (C1 _-3 alkyl) aminocarbonyl, phenyl-C1 _-3 alkylamino or № (C1 _-3 alkyl) phenyl-C1 _{- 3} alkylamino or replaced by an oxygen or sulfur atom, sulfinyl, sulfonyl, -IN-, -MS | _-3 alkyl -) -. -Mphenyl) -. -№fenil C1 _-3 alkyl -) -, -N (C1 _-3 alkylcarbonyl -) - u (C1 _-4 hydroxycarbonyl -) -, -Ν (Κ _-4 alkoxycarbonyl -) -, -N (benzoyl- ) - or -№fenil _-3 alkylcarbonyl-C1 -) -, wherein associated with the nitrogen atom of the imine tsikloalkileniminogruppy methylene group may be replaced by a carbonyl or sulphonyl group or a 5-7-membered monocyclic or condensed with a phenyl group tsikloalkileniminogruppe both related imine the nitrogen atom methylene groups in each case can be replaced by carbonyl, or

By ₆ is C1 _-4 alkyl, which is substituted by carboxy, C1 _-3 alkoxycarbonyl, aminocarbonyl, C _1-3 alkylaminocarbonyl or di- _(C1-3 alkyl) aminocarbonyl or a 4-7 membered tsikloalkileniminokarbonilnoy group, № (C1 _-3 alkyl ) - C _2-4 alkanoylamino group, which in the alkyl fragment is additionally substituted by a carboxy group or C1 _-3 alkoxycarbonyl, a group of the formula (IV), in which

K12 means a hydrogen atom, C1-6 alkyl or C3-7 cycloalkyl or substituted in the terminal position by phenyl, heteroaryl, trifluoromethyl, hydroxy group, C1-3 alkoxygroup, aminocarbonyl, C1-4 alkylaminocarbonyl, di- (C1-4 alkyl) aminocarbonyl, C1-3 alkylcarbonyl, -3alkilsulfonilaminogruppoy, № (C1 _-3 alkyl) -C1 _-3 alkylsulfonylamino, C1 _-3 alkilaminosulfonilom or di (C1-3alkyl) aminosulfonyl C 1-3 alkyl, p is the number 0, 1, 2 or 3 and

K ₁₃ takes the values of the above group K ₇ or, if p means one of the numbers 1, 2 or 3, also means a hydrogen atom, a group of the formula

-Ν ^ Μ ^ Μ ^ - ^ (V), in which

C14 means a hydrogen atom, C1-4 alkyl, C1-3 alkylcarbonyl, arylcarbonyl, phenyl-C1-3 alkyl-carbonyl, heteroarylcarbonyl, heteroaryl-C1-3 alkylcarbonyl, C1-4 alkylsulfonyl, arylsulfonyl, phenyl-C1-3 alkylsulfonyl, heteroaryl alkyl, sulfonyl, phenyl-C1-3 alkylsulfonyl, heteroaryl alkyl, sulfonyl, phenyl-C1-3 alkylsulfonyl, heteroaryl alkyl, sulfonyl, phenyl-C1-3 alkylsulfonyl, heteroaryl alkyl, sulfonyl, phenyl-C1-3 alkylsulfonyl, heteroaryl alkyl, sulfonyl, phenyl-C1-3 alkylsulfonyl, heteroaryl alkyl, sulfonyl, phenyl-C1-3 alkylsulfonyl, heteroalkyl, carbonyl, arylsulfonyl, phenyl-C1-3 alkylsulfonyl, heteroaryl alkyl, sulfonyl, arylcarbonyl

c. | means the number 1,2, 3 or 4, g means the number 1, or if with. | means one of the numbers 2, 3 or 4, means also the number 0 and

K ₁₅ takes the values of the above group K ₇ , a group of the formula ^ (K ₁₆ ) -OZ ₂ -K7 (VI), in which

K ₁₆ means a hydrogen atom or optionally substituted at the terminal position by a cyano group, a trifluoromethylcarbonylamino group or a (C1 _-3 alkyl) trifluoromethylcarbonylamino group C1 _-4 alkyl and

K17 is C1-3alkyl substituted with di (C1-3alkyl) amino-S1-3alkilkarbonilom or di- (C1-3alkyl) amino-C1 _-3 alkylsulfonyl and di- (C1 _-3 alkyl) aminocarbonyl-C1 _-3 alkyl amino, or Ν- (Κ _-3 alkyl) -C1 _- 5 alkylsulfonylamino group, or No. (C1 _-3 alkyl) phenylsulfonylamino group in which the alkyl fragment is additionally substituted with a cyano group or a carboxy group, all of which are linked by a single bond or condensed phenyl groups contained in those indicated for K ₆ residues can be mono- or disubstituted by a fluorine, chlorine, bromine or iodine atom,

C _1-5 alkyl, trifluoromethyl, hydroxy, C _1-3 alkoxy, carboxy, C _1-3 alkoxycarbonyl, aminocarbonyl, C _1-4 alkylaminocarbonyl, di- (C _1-4 alkyl) aminocarbonyl, aminosulfonyl, C _1-3 alkylaminosulfonyl , di- (C _1-3 alkyl) aminosulfonyl, C _1-3 alkylsulfonyl-79 006080 amino group, nitro group or cyano group, while the substituents can be identical or different, or two adjacent hydrogen atoms of the phenyl groups can be replaced by a methylenedioxy group, and

K ₅ means a hydrogen atom or C 1 _-3 alkyl, wherein the aryl group should be understood to be optionally mono- or disubstituted with a fluorine, chlorine, bromine or iodine atom, a cyano group, trifluoromethyl, a nitro group, a carboxy group, an aminocarbonyl, C 1-3 alkyl or C 1-3 alkoxy group phenyl or naphthyl, and the heteroaryl group should be understood as an optionally substituted monocyclic 5- or 6-membered heteroaryl group in the carbon skeleton with a C1 _-3 alkyl, and the 6-membered heteroaryl group contains one, two or three nitrogen atoms, and the 5-membered the roaryl group contains an optionally substituted C1 _-3 alkyl or phenyl-C1-3 alkyl imino group, an oxygen or sulfur atom or an optionally substituted C1-3 alkyl or phenyl C1 _-3 alkyl imino group or an oxygen or sulfur atom and additionally a nitrogen atom or an optionally substituted C1 _-3 alkyl or phenyl-C1 _-3 alkyl imino group and two nitrogen atoms, and moreover, with said monocyclic heterocyclic groups via two adjacent carbon atoms may be fused to a phenyl ring, and the bond is via a nitrogen atom yl and through the carbon atom of the heterocyclic moiety or of the condensed phenyl ring, hydrogen atoms in the indicated alkyl and alkoxy groups or in the alkyl fragments contained in the above for formula I groups can be partially or completely replaced by fluorine atoms contained in the above carboxy group residues a tert-butoxycarbonyl group, and the associated nitrogen atom, the hydrogen atom may be replaced by a hydroxy group, an acyl group, a C _1-16 alkanoyl group, an allyloxycarbonyl battening group, a C _1. ₁₆ alkoxycarbonyl group, a phenyl-C1 _-6 alkoxycarbonyl group, a C1 _-3 alkylsulfonyl-C _2-4 alkoxycarbonyl group, C _{£ -3} alkoxy-C _2-4 alkoxy-C _2-4 alkoxycarbonyl group or a group of K _e CO-O ( K _£ CK ₆ ) -O-CO-, in which Ke means _C1-8 alkyl, C _5-7 cycloalkyl, phenyl or phenyl C1 _-3 alkyl; K _£ means a hydrogen atom, C1 _-3 alkyl, C ₅ -cycloalkyl or phenyl; and K _d means a hydrogen atom, C1 _-3 alkyl or a K _e CO-O- (K _£ CK ₈ ) -O- group, in which K _e -K _d have the above values; while the amino group can also be replaced by phthalimido;

their tautomers, their diastereomers, their enantiomers, their mixtures and their salts.

2. Indolinone of General formula I according to claim 1, in which

K1 and K3 have the above values,

X means an oxygen atom

R2 is a carboxy group, a linear or branched S1-6alkoksikarbonilnuyu group, C5-7 cycloalkoxycarbonyl or phenoxycarbonyl, linear or branched S1-3alkoksikarbonilnuyu group, the alkyl moiety which is substituted in the terminal position by phenyl, heteroaryl, carboxy, C1 _-3 alkoxycarbonyl, aminocarbonyl, C1 _-3 alkylaminocarbonyl or di- (C1 _-3 alkyl) aminocarbonyl, a linear or branched C _2-3 alkoxycarbonyl group, the alkyl fragment of which is substituted in the terminal position by a chlorine atom, a hydroxy group, C _{£ - 3} alkoxy, amino, C _1-3 alkylamino or di- (C _1-3 alkyl) amino, aminocarbonyl or methylaminocarbonyl, optionally substituted in position 2 of the ethyl group with a hydroxy group or C _1-3 alkoxy, ethylaminocarbonyl or, if K ₄ is aminosulfonylphenyl or No. (C1 _-5 alkyl) C1 _-3 alkylaminocarbonylphenyl, also means di- (C1 _-2 alkyl) aminocarbonyl,

K4 is C3-7 cycloalkyl, wherein the methylene group in position 4 of a 6- or 7-membered cycloalkyl group may be substituted by an amino group, a C1-3 alkylamino group or a di- (C1-3 alkyl) amino group or be replaced by -ΝΗ or -Y (C1 _-3 alkyl ) -, or substituted by a K ₆ group, phenyl, which may additionally be mono- or disubstituted with a fluorine, chlorine or bromine atom, C _--3 alkyl, trifluoromethyl, hydroxy, C _--3 alkoxy, carboxy, C 1 _-3 alkoxycarbonyl, amino, acetylamino, aminocarbonyl, C _1-3 alkylaminocarbonyl, di (C _1-3 alkyl) and inokarbonilom, nitro or cyano group, wherein the substituents may be identical or different and

K6 means a hydrogen atom, fluorine, chlorine, bromine or iodine, cyano, nitro, amino, C1-5 alkyl, C3-7-cycloalkyl, trifluoromethyl, phenyl, tetrazolyl or heteroaryl, a group of the formula

--- CH in which the hydrogen atom bound to the nitrogen atom can be replaced by a C _1-3 alkyl, C _1-3 alkoxy group, amino C _2-3 alkoxy group, C _1-3 alkylamino C _2-3 alkoxy group, di- (C _1-3 alkyl) amino-C _2-3 alkoxy,

- 80 006080 phenyl-C1 _-3 _{alkylamino-C2-3} alkoxy, № (C1 _-3 alkyl) phenyl-C1 _-3 _{alkylamino-C2-3-alkoxy,} _{pyrrolidino-C2-3-alkoxy,} piperidino-C _2-3 C1 _-3 alkoxy or alkylmercapto, carboxy, C1 _-4 alkoxycarbonyl, aminocarbonyl, C1 _-3 alkylaminocarbonyl, phenyl-C 1 _-3 alkylaminocarbonyl or № (C1 _-3 alkyl) phenyl-C1 _-3 alkylaminocarbonyl, C _3-7 cycloalkylcarbonyl, wherein the methylene group in position 4 of a 6- or 7-membered cycloalkyl moiety may be replaced by -PN- or -N (C1 _-3 alkyl) -,

4-7-membered cycloalkylenimino group in which the methylene group bound to the imino group can be replaced by carbonyl or sulfonyl or one or two hydrogen atoms in each case can be replaced by C1 _-3 alkyl and / or in each case the methylene group in position 4 6 - or a 7-membered cycloalkylamino group may be substituted by a carboxy group, C1-3 alkoxycarbonyl, aminocarbonyl, C1-3alkylaminocarbonyl, di- (C1-3alkyl) aminocarbonyl, phenyl-C1-3alkylamino or N- (C1 _-3 alkyl) phenyl-C1 _-3 alkyl or alkylamino group or N- (C1-3 alkyl) phenyl-C1 _-3 alkyl or alkylamino group or N- (C1-3 alkyl) phenyl-C1 _-3 alkyl or alkylamino group or N- (C1-3 alkyl) phenyl-C1-alkyl; on atom oxygen and or sulfur, sulfinyl, sulfonyl, G-invariant or -N (C1 _-3 alkyl) -, substituted at the terminal position K7 C1-4 alkyl group, wherein

K7 means

S5-7tsikloalkil, wherein the methylene group in position 4 of a 6- or 7-membered cycloalkyl group may be replaced by -LN- or -N (C1 _-3 alkyl) -, or a 5-7-membered cycloalkyl group a group - (CH ₂ ) ₂ - can be replaced by the group -CO-PN-, the group - (CH ₂ ) ₃ - can be replaced by the group -НН-СО-ЫН- or the group - (СН ₂ ) ₄ - can be replaced by the group -NΗ -CO-NΗ-CO-, and in each case the hydrogen atom bound to the nitrogen atom can be replaced by a C1 _-3 alkyl, phenyl or heteroaryl, hydroxy group or C1 _-3 alkoxy group, amino group, C1 _-6 alkylamino group, di- (C1 _{- 6} alky l) amino, phenylamino, Ν-phenyl-C ^ alkylamino, phenyl-C1 _-3 alkylamino, N- (C1 _-3 alkyl) phenyl-C1 _-3 alkylamino or di (phenyl-C 1 _-3 alkyl) amino, hydroxy-t -C _2-3 alkylamino, N- (C1 _-3 alkyl) -ω-hydroxy-C _2-3 alkylamino, di- (t-hydroxy-C _2-3 alkyl) amino, di- (t- (C1 _-3 alkoxy) -C _2-3 alkyl) amino group or N- (dioxolan-2-yl) -C1 _-3 alkylamino,

C1 _-3 alkyl-carbonylamino-C _2-3 alkylamino, or C1 _-3 _{alkyl-carbonylamino-C2-3} alkyl-n- (C1 _-3 alkyl) amino,

C1 _-3 alkylsulfonylamino, N- (C1 _-3 alkyl) -C1 _-3 alkylsulfonylamino, C1 _{-3-alkylsulfonylamino} C _2-3 alkylamino or C1 _{-3-alkylsulfonylamino} C _2-3 alkyl-N- (C1 _-3 alkyl) amino , hydroxycarbonyl-C1 _-3 alkylamino or N- (C1 _-3 alkyl) hydroxycarbonyl-C1 _-3 alkylamino group, a guanidino group in which a hydrogen atom may be replaced by C 1-3 alkyl, a group of formula

-LCK8) -CO- (CH2) pK ₉ (II), in which

K8 means a hydrogen atom or C1-3 alkyl, n means one of the numbers 0, 1, 2 or 3 and

K ₉ means an amino group, a C _1-3 alkylamino group, a di- (C _1-3 alkyl) amino group, a phenylamino group, a benzylamino group or a C 1-4 alkoxy group, a 5-7-membered cycloalkylenymino group, and the methylene group at position 4 of the piperidino group can be replaced by an atom oxygen or sulfur, -CH-, -M (C1 _-3 alkyl) -, -Mphenyl) -, -P (C1 _-3 alkylcarbonyl) - or -Mbenzoyl) -, or if n is one of the numbers 1, 2 or 3 also means a hydrogen atom, a group of the formula

-K (Kyu) - (CH ₂ ) t- (CO) OK ₁₁ (III), in which

K ₁₀ means a hydrogen atom, C 1 _-3 alkyl, C 1 _-3 alkylcarbonyl or C 1 _-3 alkylsulfonyl, t means one of the numbers 1, 2 or 3, o means number 1 or, if t means one of numbers 2 or 3, it also means number 0 and

K _n means an amino group, a C1 _-3 alkylamino group, a di- (C1 _-3 alkyl) amino group, a C1 _-4 alkoxy group or a C _1-3 alkoxy-C _1-3 alkoxy group or a 5-7-membered cycloalkylene imino group, while the methylene group is in the position piperidino 4 can be replaced by oxygen or sulfur atom, -KN-, -N (C1 _-3 alkyl) -, -Mfenil) -, -P (C1 _-3 alkylcarbonyl) - or -Mbenzoil) -,

C4-7cycloalkylamino or C4-7cycloalkenylamino group in which the position 1 of the ring does not participate in the formation of a double bond,

A 4-7 membered cycloalkylenimino group in which the cycloalkylene moiety can be condensed with a phenyl group or one or two hydrogen atoms in each case can be replaced with a C _1-3 alkyl and / or methylene group at the 3-position of the pyrrolidino group is substituted by a hydroxy group or a C _1-3 alkoxy group, in each case the methylene group in position 4 of a 6- or 7-membered cycloalkylenimino group may be replaced by a hydroxy group, a hydroxy-C _1-3 alkyl, C _1-3 alkoxy group, a carboxy group, a C _1-3 alkoxycarbonyl, an aminocarbo Nil, C _1-3 alkylaminocarbonyl, di- (C1 _-3 alkyl) aminocarbonyl, phenyl-C1 _-3 alkylamino or N- (C1 _-3 alkyl) phenylC1 _-3 alkylamino or replaced by oxygen or sulfur, sulphinyl, sulfonyl, - ΝΗ-, -N (C1 _-3 alkyl) -, -N (phenyl) -, -N (phenyl-C1 _-3 alkyl -) -, -N (C1 _-3 alkylcarbonyl) -, -N (C1 _-4 alkoxycarbonyl -) -,

-Y (benzoyl) - or -Y (phenyl-C 1 _-3 alkylcarbonyl) -, while the methylene group attached to the imine nitrogen atom of the cycloalkylene amino group may be replaced by carbonyl or sulfonyl, or in a 5-6-membered monocyclic or condensed with a phenyl group the cycloalkylenimino group, both of the methylene groups bound to the imine nitrogen atom can in each case be replaced by carbonyl, or

I ₆ means C 1 _-4 alkyl, which is substituted in the terminal position by a carboxy group, C _{£ -3} alkoxycarbonyl, aminocarbonyl, C 1 _-3 alkylaminocarbonyl or di- (C 1 _-3 alkyl) aminocarbonyl or 47-membered cycloalkylenimino carbonyl group, a group of the formula

-KSCHCH-SO-SODr-Kp (IV), in which

Ryu means a hydrogen atom, C 1 _-3 alkyl, C _5-7 cycloalkyl, phenyl-C 1 _-3 alkyl or heteroaryl-C 1 _-3 alkyl, p means one of 0, 1, 2 or 3 and

K. | ₃ takes the values of the above group I ₇ or, if p means one of the numbers 1, 2 or 3, also means a hydrogen atom, a group of the formula

-M (K ₁ 4) - (SI2) _H - (CO) _G -K ₁₅ (V), in which

I ₁₄ is a hydrogen atom, C1 _-4 alkyl, C1 _-3 alkylcarbonyl, phenylcarbonyl, phenyl-C 1 _-3 alkylcarbonyl, heteroarylcarbonyl, heteroaryl-S1-3alkilkarbonil, S1-4alkilsulfonil, phenylsulfonyl, phenyl-C1 _-3 alkylsulfonyl, heteroarylsulfonyl or heteroaryl- C1 _-3 alkylsulfonyl, μ means one of the numbers 1, 2, 3 or 4, g means the number 1, or if μ means one of the numbers 2, 3 or 4, also means the number 0 and

Nu takes the values of the above group I ₇ , a group of formula

-Ν (Κ ₁₆ ) -8Ο ₂ -Κ ₁ 7 (VI), in which

K. ₁₆ means a hydrogen atom or an optionally substituted at the terminal position by a cyano group, a trifluoromethylcarbonylamino group or a (C1 _-3 alkyl) trifluoromethylcarbonylamino group C1 _-4 alkyl and

I ₁₇ means C 1 _-3 alkyl, substituted di- (C 1 _-3 alkyl) amino-C 1 _-3 alkylcarbonyl or di- (C 1 _-3 alkyl) amino-C 1 _-3 alkylsulfonyl and di- (C _1-3 alkyl) aminocarbonyl- With _1-3 alkyl, an amino group, while all connected by a simple bond or condensed phenyl groups contained in the ₆ residues indicated for I can be mono- or disubstituted by a fluorine atom, chlorine or bromine, C _{£ -3} alkyl, trifluoromethyl, hydroxy, C1 -3 alkoxy group, carboxy group, C1-3 alkoxycarbonyl, aminocarbonyl, C1-3 alkylaminocarbonyl, aminosulfonyl, C1-3 alkylaminosulfone scrap, nitro or cyano group, wherein the substituents may be identical or different, or two adjacent hydrogen atoms of the phenyl groups may be replaced by a methylenedioxy group, and

I ₅ represents a hydrogen atom or a C1 _-3 alkyl, wherein the heteroaryl group under the aforementioned should be understood optionally substituted in the carbon skeleton C1 _-3 alkyl, pyridinyl, pyrazinyl, pyrimidinyl, pyridazinyl, pyrrolyl, furyl, thienyl, oxazolyl, thiazolyl, pyrazolyl, imidazolyl or triazolyl groups in which a hydrogen atom bound to a nitrogen atom can be replaced by a C1 _-3 alkyl or phenyl-C1 _-3 alkyl, and 5-membered heteroaryl groups containing at least one imino group are linked through a carbon or nitrogen atom contained in the above residues of the carboxy group may be present as a t-butoxycarbonyl group, and the hydrogen atom bound to the nitrogen atom may be replaced by a hydroxy group, an acyl group, a C1-16 alkanoyl group, an allyloxycarbonyl group, a C ^ alkoxycarbonyl group group fenilS1 _-6 alkoxycarbonyl group, a C1 _-3 alkilsulfonilS _2-4 alkoxycarbonyl group, a C _2-4 _{£ -3} alkoksiS alkoksiS _2-4 alkoxycarbonyl group or a group of K _e CO-O- (R ₈ CH _£) -O —CO—, in which H _e means C _{£ -8} alkyl, C _5-7 cycloalkyl, phenyl or phenylCl- ₃ alkyl; I _£ means a hydrogen atom, C _{£ -3} alkyl, C _5-7 cycloalkyl or phenyl; and K ₆ means a hydrogen atom, C _{£ -3} alkyl or the group K _e CO-O- (I _£ CH ₈ ) -O-, in which I _e -K ₆ have the values indicated above; while the amino group can also be replaced by phthalimido;

- 82 006080 the hydrogen atoms in the above alkyl and alkoxy groups or in the alkyl fragments contained in the above for formula I groups can be partially or completely replaced by fluorine atoms and their tautomers, their diastereomers, their enantiomers, their mixtures and their salts.

3. Indolinone of General formula I according to claim 1, in which

X means an oxygen atom

K1 means a hydrogen atom,

K2 means a carboxy group, a linear or branched C1-4 alkoxycarbonyl group or a phenoxycarbonyl, a linear or branched C1 _-3 alkoxycarbonyl group, the alkyl fragment of which is terminally substituted with phenyl, a carboxy group, a C1-3 alkoxycarbonyl, a C1.3 alkoxycarbonyl group, a C1-3 alkyl group, a C1-3 alkoxycarbonyl group, a C1-3 alkyl group, a C1-6 alkoxycarbonyl group, a C1-3 alkyl moiety, C1-3 alkoxycarbonyl group, a C1-3 alkyl group, a C1-6 alkyloxycarbonyl group, a C1-3 alkyl moiety, a C1-6 alkoxycarbonyl group, a C1-6 alkyloxycarbonyl group, a C1-3 alkyl group, a C1-6 alkoxycarbonyl group ) aminocarbonyl, linear or branched S2-3alkoksikarbonilnuyu group, the alkyl moiety which is substituted in the terminal position by a hydroxy, C1 _-3 alkoxy, amino, C1 _-3 alkylamino or di- (C1 _-3 alkyl) amino group, aminocarbonyl or methylaminocarbonyl, optionally substituted in position 2 of the ethyl group by a hydroxy group or C1 _-3 alkoxy group of an ethylaminocarbonyl or, if K! does not mean aminosulfonylphenyl or NO (C 1 _-5 alkyl) -C 1 _-3 alkylaminocarbonylphenyl, also means di- (C 1 _-2 alkyl) aminocarbonyl,

K3 is C1-4alkyl or phenyl, which may be substituted by a fluorine, chlorine or bromine atom, trifluoromethyl, C1-3alkyl, a hydroxy group or C1-3alkoxy,

K4 S5-6tsikloalkil means, wherein the methylene group in position 4 of the cyclohexyl group may be substituted by amino, C1 _-3 alkylamino or di (C1 _-3 alkyl) amino or substituted by -N4- or -№ (S1_ ₃ alkyl) -, phenyl disubstituted with C _1-3 alkyl, C _1-3 alkoxy group or phenyl nitro group, wherein the substituents may be identical or different, or the phenyl group substituted by the K ₆ group, which may additionally be replaced by a fluorine atom, chlorine or bromine, an amino group or a nitro group, wherein

K ₆ means a fluorine, chlorine or bromine atom, a C _{! -3} alkyl, a C _{! -3} alkoxy group, a nitro group, an amino group or a C _5-6 cycloalkyl linked through a carbon atom to a pyrrolyl, pyrazolyl, imidazolyl, triazolyl or tetrazolyl group; heteroaromatic groups may be substituted in the carbon skeleton S1-3alkilom or bonded to the nitrogen atom the hydrogen atom may be replaced by C1 _-3 alkyl or phenyl-C1 _-3 alkyl, carboxy group of the formula, _{C! -4} alkoxycarbonyl, phenyl-C1 _-3 alkylaminocarbonyl or C _5-7 cycloalkylcarbonyl, 5 or 6-h the cycloalkylenimino group, the methylene group in the 4-position of the piperidino group can be replaced by an oxygen or sulfur atom, —N4- or -MS _1-3 alkyl) -, unbranched, substituted in the terminal position by the K7 C1-3 alkyl group, where

K7 means C5-7cycloalkyl, while in the 5- or 6-membered cycloalkyl group the group - (CH ₂ ) ₂ - can be replaced by the group -CO ^ H-, the group - (CH ₂ ) ₃ - can be replaced by the group - N —N — CO — N— or the group - (CH ₂ ) ₄ - can be replaced by the group —NH — CO — NH — CO — and in each case the hydrogen atom bound to the nitrogen atom can be replaced by C1 _-3 alkyl, phenyl or pyridinyl or a pyrrolyl, pyrazolyl, imidazolyl or triazolyl group bonded through a carbon or nitrogen atom; these heteroaromatic groups may be substituted in carbon a native skeleton with a C _1-3 alkyl or a hydrogen atom bound to a nitrogen atom can be replaced with a C1 _-3 alkyl, hydroxy group or a C1 _-3 alkoxy group, an amino group, a C1 _-6 alkylamino group, a di- (CI- ₆ alkyl) amino group, a phenylamino group, ^ phenyl-C _1-3 alkylamino, phenyl-C1 _-3 alkylamino or № (C1 _-3 alkyl) phenyl-C1 _-3 alkylamino, ni-hydroxy-C _2-3 alkylamino, № (C1 _-3 alkyl), hydroxy -sch -C _2-3 alkylamino, di- (y-hydroxy-C _2-3 alkyl) amino group or di- (y- (C1 _-3 alkoxy) -C _2-3 alkyl) amino group,

C1 _-3 alkylcarbonylamino-C _2-3 alkylamino or C1 _-3 alkylcarbonylamino-C _2-3 alkyl-No (C1 _-3 alkyl) amino group,

C1 _-3 alkylsulfonylamino, № (C1 _-3 alkyl) -C1 _-3 alkylsulfonylamino, alkylsulfonylamino-C1 _-3 alkylamino or _C2-3 alkylsulfonylamino-C1 _-3 alkyl, _C2-3-№ (C1 _-3 alkyl) amino,

- 83 006080 hydroxycarbonyl-C1 _-3 alkylamino or № (C1 _-3 alkyl) hydroxycarbonyl-C1 _-3 alkylamino group, a guanidino group in which a hydrogen atom may be replaced by C1 _-3 alkyl, a group of formula

-ZH8) -CO- (CH2) _P -H ₉ (II), in which

H8 means a hydrogen atom or C1-3 alkyl, η means one of the numbers 0, 1, 2 or 3 and

H ₉ means an amino group, a C1 _-3 alkylamino group, a di- (C1 _-3 alkyl) amino group or a C1 _-4 alkoxy group, a 5- or 6-membered cycloalkylamino group, and the methylene group in the 4-position of the piperidino group can be replaced by the group -ΝΉ-, -Ν (0'ι _-3 , alkyl) - or -MS | _-3 , alkylcarbonyl) -. or, if η means one of the numbers 1, 2, or 3, it also means a hydrogen atom, a group of the formula

H ₁₀ means a hydrogen atom or C 1 _-3 alkyl, t means one of the numbers 1, 2 or 3, o means the number 1, or if t means one of the numbers 2 or 3, it also means the number 0 and

Neither means an amino group, a C1 _-3 alkylamino group, a di- (C1 _-3 alkyl) amino group, a C1 _-4 alkoxy group or a methoxy-C1-3 alkoxy group or a 5- or 6-membered cycloalkylene imino group, and the methylene group in the 4-position of the piperidino group can be replaced by the group -N4-, -MC _1-3 alkyl) - or - ^ C1 _-3 alkylcarbonyl) -, azetidino group, pyrrolidino group, piperidine group, 2,6-dimethylpiperidino group, 3,5-dimethylpiperidine group or azepino group, while the methylene group in pyrene pyrrolide be substituted by a hydroxy group, methylene group in position 4 of the piperidino group, may be substituted with a hydroxy group, hydroxy-C _1-3 alkyl or C _1-3 alkoxy group or replaced by an oxygen or sulfur atom, sulfinyl, sulfonic, -N4-, -MC _1-3 alkyl) -, -MS _{1 -3} alkylcarbonyl) -, - ^ benzoyl) - or - ^ phenyl-C1 _-3 alkylcarbonyl) -, and the methylene group bound to the imine nitrogen atom of the pyrrolidino, piperidino or piperazino group may be replaced by carbonyl, or

H ₆ means straight-chain C1 _-3 alkyl, which is substituted at the terminal position with a carboxy group or C1-3 alkoxycarbonyl, a group of the formula ^ (H1 ₂ ) —CO- (CH ₂ ) p-H1e (IV), in which

H ₁₂ means a hydrogen atom, C 1 _-3 alkyl or phenyl-C 1 _-3 alkyl, p means one of the numbers 0, 1 or 2 and

H ₁₃ is amino, C _1-4 alkylamino, di- (C _1-4 alkyl) amino, benzylamino, № (C1 _-3 alkyl) benzylamino, C1 _-3 alkoxy-C1 _-3 alkylamino, № (C1 _-3 alkyl) -C1 _-3 alkoxy-C1 _-3 alkylamino, di (2-methoxyethyl) amino, di- (w-hydroxy-C _2-3 alkyl) amino group or aminocarbonylmethyl-№ (methyl) amino group bonded via the nitrogen atom, optionally substituted with C1 _-3 alkyl pyrrolyl, pyrazolyl or imidazolyl group, pyrrolidino group, piperidino group, morpholino group, thiomorpholino group or an optionally substituted in position 4, C1-3alkyl, phenyl-C1-3alkyl, C1-3 alkylcarbonyl or C1-4alkoxycarbonyl piperazino group or, if η means the number 1 or 2, also means a hydrogen atom, a group of the formula ^ (HmISN ^ -CO2) ^ (V) , wherein

H14 means a hydrogen atom, C1-4 alkyl, C1-3 alkylcarbonyl, phenylcarbonyl, phenyl-C1-3 alkylcarbonyl, furylcarbonyl, pyridinylcarbonyl, furyl-C1-3 alkylcarbonyl, pyridinyl-C1-3 alkylcarbonyl, C1 _-4 alkylsulfonyl, phenylsulfonylsulfonylsulfonylsulfonylsulfons _{. 3} alkylsulfonyl,

c. | means one of the numbers 1, 2 or 3, g means the number 1 or, if c. | means one of the numbers 2 or 3, means also the number 0 and

H15 means an amino group, a C1 _-4 alkylamino group, a di- (C1 _-4 alkyl) amino group, a phenylamino group, a (C1 _-4 alkyl) phenylamino group, a benzylamino group or a (C1 _-4 alkyl) benzylamino group, or a group of the formula ^ (H ₁₆ ) - 8O ₂ -N ₁₇ (VI), in which

- 84 006080

The ₁₆ stands for a hydrogen atom or optionally substituted at the terminal position with cyano, or triftormetilkarbonilaminogruppoy № (C1 _-3 alkyl) triftormetilkarbonilaminogruppoy C1 _-s alkyl and

B ₁₇ means C1 _-3 alkyl, with all the simple bonded or condensed phenyl groups contained in the B ₆ residues indicated for being substituted by a fluorine, chlorine or bromine atom, methyl, trifluoromethyl, methoxy, nitro or cyano, and

B5 means a hydrogen atom, wherein the hydrogen atom, which in the above residues is in each case bound to the nitrogen atom, may be replaced by acetyl or t-butoxycarbonyl, and the carboxy group contained in the above residues may also be present as the t-butoxycarbonyl group of the precursor, their tautomers, their diastereomers, their enantiomers, their mixtures and their salts.

4. Indolinone of General formula I according to claim 1, in which

X means an oxygen atom

B1 and B5 each means a hydrogen atom,

₂ means methoxycarbonyl, ethoxycarbonyl or aminocarbonyl,

B3 means phenyl and

B4 means monosubstituted group B6 phenyl, where

In ₆ means No. Methylimidazol-2-yl, unbranched C1 _-3 alkyl, which is substituted in the terminal position of the C1 _-4 alkylamino group, di- (C1 _-4 alkyl) amino group, piperidino or 2,6-dimethylpiperidino, group of the formula

LH ^ -SODR-Bb (IV), in which

_B12 is C1 _-3 alkyl, p denotes one of the numbers 1 or 2 and

In ₁₃ means a di- (C1 _-3 alkyl) amino group, or a group of the formula

- ЖВ ^ МСШМСОХ-Вв (V), in which

B _{1 4} means C 1 _-3 alkylcarbonyl or C 1 _-3 alkylsulfonyl,

₁₅ means di- (C _{! -3} alkyl) amino group, their tautomers, their diastereomers, their enantiomers, their mixtures and their salts.

5. Substituted indolinones of general formula I according to claim 1 from the group comprising (a) 3-Ζ- [1 - (4- (piperidin-1-methyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone , (b) 3-Ζ- [1 - (4- (piperidin-1-ylmethyl) anilino) -1-phenylmethylene] -6-carbamoyl-2-indolinone, (c) 3-Ζ- [1 - (4- ((piperidin-1-methylmethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone, (g) 3 ^ - [1- (4- (dimethylaminomethyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl- 2-indolinone, (d) 3-Ζ- [1 - (4 - ((2,6-dimethylpiperidin-1-yl) methyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2indolinone, (e) 3 - Ζ- [1 - (4- (No. (2-dimethylaminoethyl) -Noacetylamino) anilino) -1-Fe nilmethylene] -6-ethoxycarbonyl-2-indolinone, (g) 3 -Ζ- [1 - (4- (Ν- (3-dimethylaminopropyl) -Naacetylamino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2- indolinone, (h) 3 ^ - [1- (4- (no. (2-dimethylaminoethyl) -Nomethylsulfonylamino) anilino) -1-phenylmethylene] -6 ethoxycarbonyl-2-indolinone, (and) 3 ^ - [1- (4 - (dimethylaminomethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone, (k) 3 -Ζ- [1 - (4- (№ acetyl-№dimethylaminocarbonylmethylamino) anilino) -1-phenylmethylene] -6- methoxycarbonyl-2-indolinone, (l) 3-Ζ- [1 - (4-ethylaminomethylanilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone, (m) 3 -Ζ- [1- (4- (1 -methylimidazole-2 -yl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone, (n) 3 -Ζ- [1 - (4- (No. of dimethylaminomethylcarbonyl-No.methylamino) anilino) -1-phenylmethylene] -6methoxycarbonyl-2 α-indolinone, (o) 3 -Ζ - [1 - (4- (No. (2-dimethylaminoethyl) -Nomethylsulfonylamino) anilino) -1-phenylmethylene] -6methoxycarbonyl-2-indolinone, (n) 3 -Ζ- [1 - (4- (Ν- (3-dimethylaminopropyl) -Nomethylsulfonylamino) anilino) -1-phenylmethylene] -6methoxycarbonyl-2-indolinone, (p) 3 -Ζ- [1- (4- (No.dimethylaminocarbonylmethyl-No.methylsulfonylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone,

- 85 006080 (s) 3 -Ζ- [1- (4- (K ((2-dimethylaminoethyl) carbonyl) -Nmethylamino) anilino) -1-phenylmethylene] -6methoxycarbonyl-2-indolinone, (t) 3 -Ζ - [1 - (4- (K (2-dimethylaminoethyl) -Cacetylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone and (y) 3-Ζ- [1- (4-methylaminomethylanilino) -1 -phenylmethylene] -6-methoxycarbonyl-2-indolinone, (f) 3 -Ζ- [1- (4- (K ((4-methylpiperazin-1-yl) methylcarbonyl) -Cmethylamino) anilino) -1-phenylmethylene] - 6-methoxycarbonyl-2-indolinone, their tautomers, their mixtures and their salts.

6. Physiologically acceptable salts of the compounds according to any one of claims 1 to 5.

7. A drug containing a compound according to any one of claims 1 to 5 or a salt according to claim 6 and optionally one or more inert carriers and / or diluents.

8. The use of a compound according to any one of claims 1 to 5 or a salt according to claim 6 for the manufacture of a medicament suitable for the treatment of excessive or abnormal cell proliferation.

9. The method of obtaining a medicinal product according to claim 7, characterized in that the compound according to any one of claims 1 to 5 or the salt according to claim 6 in a non-chemical manner combined with one or more inert carriers and / or diluents.

10. The method of producing compounds according to any one of claims 1 to 6, characterized in that the compound of the general formula (VII), in which

X and K ₃ have the values specified in claims 1-5,

K ₂ 'has the values indicated for K ₂ in claims 1-5,

Ζ ₁ means a halogen atom, a hydroxy, alkoxy or arylalkoxy group, is reacted with an amine of the general formula in which

K ₄ and K ₅ have the meanings indicated in claims _1-5 , and then, if necessary, the protective group used for the nitrogen atom of the lactam group or the compound obtained in this way is separated off from the solid phase, and if necessary, the compound of general formula I thus obtained containing an alkoxycarbonyl group is transferred by hydrolysis to the corresponding carboxy-compound, or a compound of the general formula I obtained in this way, containing an amino or alkylamino group, is converted by hydroalkylation into the corresponding its alkylamino or dialkylamino compound, or the compound of general formula I obtained in this way, containing an amino or alkylamino group, is transferred by acylation or sulfonation to the corresponding acyl or sulfonyl compound, or the compound of general formula I obtained in this way, containing carboxy group, is transferred by esterification or amidation to the corresponding ester or aminocarbonyl compound, or the compound of the general formula I thus obtained, containing a cycloalkylenimino group in which the methylene group is replaced by a sulfur atom, transferred by oxidation to the corresponding sulfinyl or sulfonyl compound, or the compound of general formula I obtained in this way, containing the nitro group, is transferred by reduction to the corresponding amino compound, or the compound of general formula I obtained in this way, in which K is substituted by an amino, alkylamino, aminoalkyl or Ν-alkylamino group phenyl, translated by reacting with the appropriate cyanate, isocyanate or carbamoylg ogenidom a corresponding urea compound of general formula I, or

- 86 006080 A compound of the general formula I obtained in this way, in which B ₄ is phenyl substituted by an amino group, an alkylamino group, an aminoalkyl or α-alkylamino group, is transferred by reacting with an appropriate amidino-transmitting compound or by reacting with an appropriate nitrile to the corresponding guanidine compound of general formula I, or if necessary, remove the protective group used during the reactions to protect the reactive groups, or if necessary then obtained in this way The compound of general formula I is divided into its stereoisomers, or the compound of general formula I thus obtained is transferred to one of its salts, primarily for pharmaceutical use, to one of its physiologically acceptable salts with an inorganic or organic acid or an inorganic or organic base.

11. The method of producing compounds of general formula I according to any one of claims 1 to 6, in which B ₂ has the meanings indicated in claims 1 to 5, with the exception of the carboxy group, characterized in that the compound of the general formula in which

AT! and B ₃ -B ₅ have the meanings indicated in claims _1-5 , or its reactive derivatives are reacted with a compound of the general formula

Η-B ^ (X) in which

B19 S1-6alkanol means, S4-7tsikloalkanol or aromatic alcohol S1-6alkanol, the alkyl moiety of which is substituted in the terminal position by phenyl, heteroaryl, carboxy, C1-3 alkoxycarbonyl, aminocarbonyl, S1-3alkilaminokarbonilom or di- (C1-3alkyl) aminocarbonyl,

C 2-6 alkanol, the alkyl fragment of which is substituted in the terminal position by a chlorine atom, a hydroxy group, a C 1-3 alkoxy group, an amino group, a C 1-3 alkylamino group or a di (C 1-3 alkyl) amino group, an amino group or a methylamino group, optionally substituted in position 2 of the ethyl group by a hydroxy group or C _{1 -3} alkoxy group of an ethylamino group or a di- (C _1-2 alkyl) amino group, and if necessary after this, a compound of the general formula I obtained in this way, containing an alkoxycarbonyl group, is transferred by hydrolysis to the corresponding carboxylate The injection, or the compound of the general formula I obtained in this way, containing an amino or alkylamino group, is converted by hydroalkylation to the corresponding alkylamino or dialkylamino compound, or the compound of general formula I obtained in this way, containing the amino or alkylamino group, is converted by acylation or sulfonation into the corresponding acyl acid. or a sulfonyl compound, or a compound of the general formula I obtained in this way, containing a carboxy group, is converted by esterification or amidation to the corresponding its ester or aminocarbonyl compound, or the compound of the general formula I obtained in this way, containing a cycloalkylenimino group in which the methylene group is replaced by a sulfur atom, is converted by oxidation to the corresponding sulfinyl or sulfonyl compound, or the compound of the general formula I thus obtained containing the nitro group is transferred by reduction to the corresponding amino compound, or a compound of the general formula I thus obtained, in which it is a substituted amino group, and by a phenylamino group, an aminoalkyl or алки-alkylamino group, is transferred by reacting with an appropriate cyanate, isocyanate or carbamoyl halide into the corresponding urea compound of general formula I, or the compound of general formula I obtained in this way, in which B ₄ is a substituted amino group, alkylamino group, amino alkyl, or -alkylamino phenyl, translated by reacting with an appropriate amidino group transmitting compound or by reacting with an appropriate nitrile in accordance with uyuschee guanidinosoedinenie general formula I, or

- 87 006080 if necessary, remove the protective group used during the reactions to protect the reactive groups, or if necessary then the compound of the general formula I thus obtained is divided into its stereoisomers, or the compound of the general formula I obtained in this way is transferred to one of its salts before In total for pharmaceutical application in one of its physiologically acceptable salts with inorganic or organic acid or inorganic or organic base.

12. The method of obtaining compounds of General formula I, in which K is substituted by a group of K ₇ C1 _-4 alkyl, where

K is amino, C ^ alkylamino, di- (C1 _-7 alkyl) amino, phenylamino, №fenil C1 _-3 alkylamino, phenyl-C1 _-3 alkylamino, № (C1 _-3 alkyl) phenyl-C1 _-3 alkylamino or di - (phenyl-C1 _-3 alkyl) amino, w-hydroxy-C _2-3 alkylamino, № (C1 _-3 alkyl) -o> _{-hydroxy-C2-3-alkylamino,} di- _{(w-hydroxy-2- 3} alkyl) amino group, di- (w- (C1 _-3 alkoxy) -C _2-3 alkyl) amino group or no. (Dioxolan-2-yl) -C1 _-3 alkylamino group,

C1 _-3 alkyl-carbonylamino-C _2-3 alkylamino, or C1 _-3 _{alkyl-carbonylamino-C2-3} alkyl-H- (C1 _-3 alkyl) amino,

C1 _-3 alkylsulfonylamino, № (C1 _-3 alkyl) -C1 _-3 alkylsulfonylamino, _{C! -3-alkylsulfonylamino} C _2-3 alkylamino, or C1 _{-3-alkylsulfonylamino} C _2-3 alkyl-H- (C1 _-3 alkyl) amino , a group of the formula ^ (K0) - (CH ₂ MSO) o-K1 (III), in which Ko means a hydrogen atom, C1 _-3 alkyl, C1 _-3 alkylcarbonyl, arylcarbonyl, phenyl-C1 _-3 alkylcarbonyl, C1 _-3 alkylsulfonyl , arylsulfonyl or phenyl-C1 _-3 alkylsulfonyl, t means one of the numbers 1, 2, 3 or 4, o means the number 1 and

K11 is an amino group, S1-4alkilaminogruppu, di- (C1-4alkyl) amino, phenylamino, № (C1 _-4 alkyl), phenylamino, benzylamino, № (C1 _-4 alkyl) benzylamino, C1 _-4 alkoxy-C1 S1-3alkoksi A 3 alkoxy group optionally substituted in the 1 position with a C1-3 alkyl di (C1-4 alkyl) amino C _1-3 alkylamino group or a 4-7 membered cycloalkylenyl amino group, wherein the cycloalkylene moiety can be condensed with a phenyl ring or in each case a methylene group in position 4 of the 6- or 7-membered cycloalkylenimino group can be replaced by an oxygen atom or sulfur atom, sulfinyl, sulfonyl, -№N--and (C1 _-3 alkyl) -, u (phenyl) -, u (C1 _-3 alkylcarbonyl) - or -N (benzoyl) -,

C4-7cycloalkylamino, C4-7cycloalkyl-C1-3alkylamino or C4-7cycloalkenylamino group in which the position 1 of the ring does not participate in the formation of a double bond, while the above groups in each case can additionally be replaced at the amine nitrogen atom by C5-7cycloalkyl, C2 -4 alkenyl or C1-4 alkyl, or

4-7-membered cycloalkylamino group in which the cycloalkylene moiety can be condensed with a phenyl group or with an oxazolo, imidazolo, thiazolo, pyridino, pyrazino or pyrimidine group, optionally substituted by a fluorine atom, chlorine, bromine or iodine, nitro group, C _{1-3 with} alkyl, C _1-3 alkoxy group or amino group, and / or one or two hydrogen atoms in each case can be replaced with C1 _-3 alkyl, C _5-7 cycloalkyl or phenyl and / or methylene group in position 3 5- the cycloalkenyl-amino group may be substituted by a hydroxy group, hydroxy-C1 _-3 alkyl, C1 _-3 alkoxy or C1 _-3 alkoxy-C1 _-3 alkyl, in each case a methylene group in position 3 or 4, 6- or 7-membered tsikloalkileniminogruppy may be substituted with hydroxy, hydroxy-S1-3alkilom, S1-3alkoksigruppoy, S1-3alkoksiS1-3alkilom, S1-4alkoksikarbonilom, aminocarbonyl, S1-3alkilaminokarbonilom, di- (C1-3alkyl) aminocarbonyl, phenyl-C1 _-3 alkylamino or № (C1 _-3 alkyl) phenyl-C1 _-3 alkylamino or replaced by an oxygen atom or sulfur atom, sulfinyl, sulfonyl, -№N--and (C1 _-3 alkyl -) -, u (phenyl) -, H (phenyl-C1 _-3 alkyl -) -, -H (C1 _-3 alkylcarbonyl -) - u (C1 _-4 alkoxycarbonyl -) -, -N (benzoyl -) - or -N (fenilS1-3alkilkarbonil -) -, wherein associated with the nitrogen atom tsikloalkileniminogruppy imine methylene group may be replaced on a carbonyl or sulfonyl, or in a 5–7-membered monocyclic or cycloalkylamino group condensed with a phenyl group, both methylene groups bound to the imine nitrogen atom can be replaced in each case by a carbonyl, characterized in that the compound of the general formula

- 88 006080 in which

K ₃ , K ₅ and X have the meanings indicated in claims _1-5 ,

K ₂ 'has the values indicated for K ₂ in claims 1-5,

K. | ₈ means a hydrogen atom or a protective group for the nitrogen atom of the lactam group, wherein one of the residues K ₂ and K ₁₈ may also be an bond with the solid phase, optionally formed by a spacer, and the other of the residues K / and K ₁₈ has the above values,

And mean C1 _-4 alkyl and

Ζ2 means a leaving group, is reacted with an amine of the general formula

11-K (XII), in which

K ₇ ′ is as described above for K ₇ , and then, if necessary, the protective group for the nitrogen atom of the lactam group used is cleaved, or the compound thus obtained is separated from the solid phase and, if necessary, the compound of general formula I obtained in this way, containing an alkoxycarbonyl group by hydrolysis to the corresponding carboxy compound, or the compound of the general formula I obtained in this way, containing an amino or alkylamino group, is converted by hydroalkylation to the corresponding the alkylamino or dialkylamino compound, or the compound of the general formula I obtained in this way, containing an amino or alkylamino group, is transferred by acylation or sulfonation to the corresponding acyl or sulfonyl compound, or the compound of general formula I obtained in this way, containing a carboxy group, is transferred by esterification or amidation to the corresponding ester or aminocarbonyl compound, or the compound of the general formula I thus obtained, containing a cycloalkylamino group in which the methylene group is replaced by a sulfur atom, transferred by oxidation to the corresponding sulfinyl or sulfonyl compound, or the compound of general formula I obtained in this way, containing the nitro group, is transferred by reduction to the corresponding amino compound, or the compound of general formula I obtained in this way, in which K is substituted by an amino, alkylamino, aminoalkyl or Ν-alkylamino group phenyl, translated by reacting with the appropriate cyanate, isocyanate or carbamoylg logide to the corresponding urea compound of general formula I, or the compound of general formula I obtained in this way, in which K represents a substituted amino group, an alkylamino group, an aminoalkyl, or an Ν-alkylamino group of phenyl, is transferred by reacting with an appropriate amidino group or by reacting with an appropriate nitrile to the corresponding a guanidine compound of general formula I, or, if necessary, cleave the protective group used during the reactions to protect the reactive or, if necessary, the compound of the general formula I thus obtained is divided into its stereoisomers, or the compound of the general formula I thus obtained is transferred to one of its salts, primarily for pharmaceutical use to one of its physiologically acceptable salts from inorganic or organic acid or inorganic or organic base.

13. The compound according to claim 5, which is 3 ^ - [1- (4- (No. ((4-methylpiperazin-1-yl) methylcarbonyl) -Y-methylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl- 2-indolinone or its pharmaceutically acceptable salt.